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THE  ELEMENTS 


OF   THE 


SCIENCE  of  NUTRITION 


BY 

GRAHAM  LUSK,  Ph.D.,  Sc.D.,  F.R.S.  (Edin.) 

PROFESSOR     OF     PHYSIOLOGY     AT     THE     CORNELL     UNIVERSITY      MEDICAL     COLLEGE, 
NEW    YORK    CITY 


THIRD  EDITION,  RESET 


PHILADELPHIA  AND   LONDON 

W.    B.    SAUNDERS    COMPANY 

1917 


Copyright,  1906,  by  W.  B.  Saunders  Company.    Revised,  entirely  reset,  reprinted,  and 

recopyrighted  November,  1909.    .Revised,  entirely  reset,  reprinted, 

and  recopyrighted  June,  1917 


Copyright   191 7,  by  W.  B.  Saunders  Company 


Q? 


4-\ 


\_<^1 


PRINTED    IN    AMERICA 

PRESS    OF 

W.     B.     SAUNDERS     COMPANY 

PHILADELPHIA 


TO  THE  MEMORY  OF 
CARL  VON  VOIT 

MASTER  AND  FRIEND 

FROM  WHOM  THE  AUTHOR  RECEIVED  THE  INSPIRATION 

OF  HIS  LIFE'S  WORK 

THIS  VOLUME  IS  DEDICATED 


"The  greatest  joy  of  those  who  are  steeped  in  work  and  who 
have  succeeded  in  finding  new  truths  and  in  understanding  the 
relations  of  things  to  each  other,  lies  in  work  itself." 

Carl  von  Voit. 


PREFACE  TO  THE  THIRD    EDITION 


In  the  preparation  of  the  first  edition  of  this  book  a  decade 
ago  the  endeavor  was  made  to  admit  to  the  introductory 
chapter  only  such  material  as  appeared  to  be  susceptible  of 
scientific  proof  and  to  make  it  the  key  to  the  rest  of  the  book. 
In  this,  the  third  edition,  that  chapter  remains  virtually  un- 
changed. The  rest  of  the  book  shows  many  important  addi- 
tions to  the  facts  of  metabolism  and  revisions  of  its  theories. 

The  aim  of  the  book  remains  the  same,  to  review  the 
scientific  substratum  upon  which  rests  present-day  knowledge 
of  nutrition  both  in  health  and  in  disease.  Throughout,  no 
statement  has  been  made  without  endeavoring  to  examine 
the  evidence  on  which  it  is  based. 

Laboratory  methods  to  explain  the  inner  processes  in  dis- 
ease have  been  applied  to  hospital  patients  for  thirty  years 
or  more  in  Germany.  In  the  United  States  great  advances 
have  lately  been  accomplished  in  this  direction.  If  such  in- 
vestigations are  still  further  promoted  by  their  discussion 
here,  this  writing  will  not  have  been  in  vain. 

The  author  would  apologize  to  all  whose  claims  of  priority 
of  discovery  have  not  been  duly  recognized. 

He  gratefully  acknowledges  the  helpful  criticism  of  all 
those  who  have  been  his  fellow-workers  in  the  laboratory, 
especially  John  R.  Murlin,  E.  F.  DuBois,  and  A.  I.  Ringer, 
who  for  periods  of  several  years  have  been  closely  associated 
with  him.  He  would  also  express  his  appreciation  of  the 
generous  support  of  the  experimental  work  in  his  laboratory 
by  the  authorities  of  the  Cornell  Medical  College,  as  well  as 

13 


14  PREFACE 

by  Mrs.  Russell  Sage  and  the  Trustees  of  the  Russell  Sage 
Institute  of  Pathology. 

It  is,  furthermore,  a  privilege  to  recognize  the  great  influ- 
ence which  a  personal  acquaintance  with  such  men  as  F.  G. 
Benedict  and  S.  R.  Benedict,  Cathcart,  Chittenden,  Cremer, 
Dakin,  Folin,  Halliburton,  Hopkins,  Kossel,  Levene,  Magnus- 
Levy,  Lafayette  Mendel,  Friedrich  von  Miiller,  von  Noorden, 
Rubner,  E.  Voit,  and  Zuntz  has  had  upon  the  conceptions  of 
the  subject  of  nutrition  as  set  down  in  this  book. 

He  wishes  to  express  his  great  obligation  to  a  former  pupil, 
Dr.  Margaret  B.  Wilson,  who  has  painstakingly  corrected  and 
improved  the  manuscript  and  proof. 

He  is  indebted  to  Dr.  F.  C.  Gephart  for  the  preparation 
of  the  index. 

Finally,  the  writer  desires  to  state  that  he  has  no  inten- 
tion of  again  revising  this  book.  In  another  decade  the  de- 
velopment of  scientific  knowledge  will  probably  permit  the 
formulation  of  the  subject  from  the  standpoint  of  physical 
chemistry.  It  cannot  now  be  so  treated.  The  field  is  open. 
That  the  joy  of  the  labor  may  be  as  great  to  him  who  next 
reviews  the  subject  as  it  has  been  to  the  writer,  is  the  earnest 
wish  of 

Graham  Lusk. 

Physiological  Laboratory, 
Cornell  University  Medical  College, 

New  York  City. 
June,  1917. 


CONTENTS 


CHAPTER  I  page 

Introductory 1 7 

CHAPTER  II 
The  Atwater-Rosa  Respiration  Calorimeter 56 

CHAPTER  III 
Starvation 69 

CHAPTER  IV 

The  Regulation  of  Temperature 114 

CHAPTER  V 

The  Influence  of  Protein  Food — Part  I.     Nitrogen  Equilibrium .. .   152 

CHAPTER  VI 

The    Influence    of    Protein    Food — Part   II.    The    Intermediary 
Metabolism 171 

CHAPTER  VII 

The    Influence    of    Protein    Food — Part    III.    The    Respiratory 
Metabolism 223 

CHAPTER  VIII 

The  Influence  of  the  Ingestion  of  Fat. 248 

CHAPTER  IX 

The  Influence  of  the  Ingestion  of  Carbohydrate — Part  I.    The 

Intermediary  Metabolism 258 

CHAPTER  X 

The  Influence  of  the  Ingestion  of  Carbohydrate — Part  II.    The 

Respiratory  Metabolism 289 

15 


1 6  CONTENTS 

CHAPTER  XI 

PAGE 

The  Influence  of  Mechanical  Work  on  Metabolism 309 

CHAPTER  XII 
A  Normal  Diet 334 

CHAPTER  XIII 

The  Nutritive  Value  of  Various  Materials  Used  as  Foods 362 

CHAPTER  XIV 
The  Food  Requirement  During  the  Period  of  Growth 379 

CHAPTER  XV 

Metabolism  in  Anemia,  at  High  Altitudes,  in  Myxedema  and  in 
Exophthalmic  Goiter 418 

CHAPTER  XVI 

Metabolism  in  Diabetes  and  in  Phosphorus-poisoning 445 

CHAPTER  XVII 

Metabolism  in  Nephritis,  in  Cardiac  Disease,  and  in  Other  Cases 
Involving  Acidosis 495 

CHAPTER  XVIII 
Metabolism  in  Fever 499 

CHAPTER  XIX 
Purin  Metabolism — Gout 526 

CHAPTER  XX 

The  Influence  of  Certain  Drugs  Upon  Metabolism 553 

CHAPTER  XXI 

Food  Economics 555 

Appendlx 573 

Index 5^5 


THE  ELEMENTS  OF  THE   SCIENCE 
OF  NUTRITION 


CHAPTER  I 

INTRODUCTORY 

The  earliest  scientific  observations  concerning  nutrition 
were  founded  upon  the  commonly  noted  fact  that  in  spite  of 
the  ingestion  of  large  quantities  of  food,  a  normal  man  did  not 
vary  greatly  in  size  from  year  to  year.  It  was  understood 
early  in  the  history  of  physiology  that  the  weight  added  by 
the  ingestion  of  food  and  drink  was  lost  in  the  urine,  the  feces, 
and  the  "insensible  perspiration."  The  "insensible  perspira- 
tion" was  partly  in  evidence  when  moisture  of  the  warm 
breath  condensed  upon  a  cold  plate.  By  it  were  meant  the 
usually  invisible  exhalations  from  the  body,  which  are  now 
known  to  be  carbon  dioxid  and  water. 

Sanctorius1  made  many  experiments  upon  himself  and 
others  to  determine  the  amount  of  insensible  perspiration. 
An  old  cut  shows  him  sitting  in  a  chair  suspended  from  a  large 
steelyard.  As  a  matter  of  routine  he  determined  his  own 
weight  previous  to  each  meal  and  then  weighted  the  steelyard 
so  as  to  counterbalance  the  additional  food  he  proposed  to  eat. 
During  the  meal  when  the  chair  dipped  he  ended  his  repast. 

In  Section  I,  Aphorism  II,  Sanctorius  gives  the  following 
curious  advice:  "If  a  physician  who  has  the  care  of  another's 
health  is  acquainted  only  with  the  sensible  supplies  and  evac- 
uations, and  knows  nothing  of  the  waste  that  is  daily  made  by 

1  Sanctorius:  "De  medicina  statica  aphorismi,"  Venice,  1614.  Trans- 
lation by  John  Quincy,  M.D.,  London,  1737. 

2  17 


1 8  SCIENCE    OF    NUTRITION 

the  insensible  perspiration,  he  will  only  deceive  his  patient 
and  never  cure  him."  Aphorism  III  reads:  "He  only  who 
knows  how  much  and  when  the  body  does  more  or  less  in- 
sensibly perspire  will  be  able  to  discern  when  or  what  is  to  be 
added  or  taken  away  either  for  the  recovery  or  preservation  of 
health." 

In  1668  John  Mayow,  writing  in  London,  stated  that  the 
atmosphere  contained  a  constituent  which  supported  combus- 
tion as  well  as  animal  life. 

The  modern  era  of  the  science  of  nutrition  was  opened  by 
Lavoisier  in  1780.  He  was  the  first  to  apply  the  balance  and 
the  thermometer  to  the  investigation  of  the  phenomena  of 
life,  and  he  declared  "La  vie  est  une  fonction  chimique." 
The  work  of  today  is  but  the  continuation  of  that  done  a 
century  and  more  ago.  Lavoisier  and  Laplace  made  experi- 
ments on  animal  heat  and  respiration.  The  great  German 
chemist  Liebig  received  his  early  training  in  Paris,  residing 
there  in  1822.  Liebig's  conception  of  the  processes  of  nutrition 
fired  the  genius  of  Voit  to  the  painstaking  researches  which 
laid  the  foundation  of  his  Munich  school.  These  have  been 
repeated  and  extended  by  his  pupils,  of  whom  Rubner  is 
chief,  and  by  others  the  world  over.  Thus  the  knowledge 
often  transmitted  personally  from  the  master  to  the  pupil,  to 
be  in  turn  elaborated,  had  its  seed  in  the  intellect  of  Lavoisier. 
It  was  he  who  first  discovered  the  true  importance  of  oxygen 
gas,  to  which  he  gave  its  present  name.  He  declared  that 
life  processes  were  those  of  oxidation,  with  the  resulting 
elimination  of  heat.  He  believed  that  oxygen  was  the  cause 
of  the  decomposition  of  a  fluid  brought  to  the  lungs,  and  that 
hydrogen  and  carbon  were  produced  in  this  fluid  and  then 
united  with  oxygen  to  form  water  and  carbon  dioxid.  He 
said  that  perspiration  regulated  the  quantity  of  heat  lost  from 
the  body  and  that  digestion  replenished  the  blood  with  the 
materials  eliminated  through  respiration  and  perspiration. 
It  was  he  who  first  made  respiration  experiments  on  man,  the 
results  of  which  are  briefly  described  in  a  letter  to  Monsieur 


INTRODUCTORY  1 9 

Terray,1  written  in  Paris  and  dated  November  19,  1790. 
There  is  no  existing  record  of  the  apparatus  with  which 
Lavoisier  worked  and  early  obtained  the  following  results. 
The  more  important  conclusions  Lavoisier  sums  up  as  follows : 

1 .  The  quantity  of  oxygen  absorbed  by  a  resting  man  at  a 

temperature  of   2  6°   C.   is   1200  pouces  de  France2 
hourly. 

2.  The  quantity  of  oxygen  required  at  a  temperature  of 

120  C.  rises  to  1400  pouces. 

3.  During  the  digestion  of  food  the  quantity  of  oxygen 

amounts  to  from  1800  to  1900  pouces. 

4.  During  exercise  4000  pouces  and  over  may  be  the 

quantity  of  oxygen  absorbed. 

These  remarkable  results  are  in  strict  accord  with  the 
knowledge  of  our  own  day.  We  know  more  details,  but  the 
fundamental  fact  that  the  quantity  of  oxygen  absorbed  and 
of  carbon  dioxid  excreted  depends  primarily  on  (1)  food,  (2) 
work,  and  (3)  temperature  was  established  by  Lavoisier  with- 
in a  few  years  after  his  discovery  that  oxygen  supported 
combustion.  Writing  in  1849  Regnault  and  Reiset  say, 
"Les  recherches  modernes  ont  confirm  e  ces  vues  profondes 
de  l'illustre  savant." 

It  was,  however,  quickly  noted  that  if  carbon  and  hydrogen 
burned  in  the  lungs,  the  greatest  heat  would  be  developed 
there,  a  result  not  in  accordance  with  observation.  It  was 
then  suggested  that  the  blood  dissolved  oxygen,  and  that  the 
production  of  carbon  dioxid  and  water  took  place  through 
oxidation  within  the  blood.  In  1837  Magnus  discovered  that 
the  blood  did  hold  large  quantities  of  oxygen  and  carbon 
dioxid,  which  gave  apparent  support  to  this  theory.  Ludwig 
in  his  later  years  believed  that  the  oxidation  took  place  in  the 
blood.3  Through  the  critical  studies  of  Liebig,  which  were 
published  in  1842,  it  was  seen  that  it  was  not  carbon  and 

1  Report  of  the  British  Association  for  the  Advancement  of  Science,  Edin- 
burgh, 1871,  p.  189. 

2 1  cubic  pouce  =  0.0198  liter. 
3  Oral  statement  to  the  writer. 


20  SCIENCE    OF    NUTRITION 

hydrogen  which  burned  in  the  body,  but  protein,  carbohy- 
drates, and  fat.  Liebig's  original  theory  was  that  while 
oxygen  caused  the  combustion  of  fat  and  carbohydrates,  the 
breaking  down  of  protein  was  caused  by  muscle  work.  It 
will  be  shown  later  that  oxygen  is  not  the  cause  of  the  de- 
composition of  materials  in  the  body,  but  that  this  decomposi- 
tion proceeds  from  unknown  causes,  and  the  products  involved 
unite  with  oxygen.  The  sum  of  these  chemical  changes  of 
materials  under  the  influence  of  living  cells  is  known  as 
metabolism.  This  process  may  involve  two  factors,  catabolism, 
or  the  reduction  of  higher  chemical  compounds  into  lower, 
and  anabolism,  or  the  construction  of  higher  substances  from 
lower  ones. 

Liebig  was  also  the  father  of  the  modern  methods  of  organic 
analysis,  and  with  him  began  the  great  accumulation  of  knowl- 
edge concerning  the  chemistry  of  the  carbon  compounds, 
including  many  products  of  the  animal  economy.  These 
discoveries  gave  the  world  a  knowledge  of  the  constitution 
of  foods,  of  urine,  of  feces,  and  of  tissues,  which  was  not 
possessed  by  Lavoisier. 

Liebig  applied  to  the  problems  of  biology  the  mental 
wealth  of  the  newer  chemistry  which  he  himself  was  creating. 
He  knew  that  protein  contained  nitrogen,  and  in  1842  he  sug- 
gested that  the  nitrogen  in  the  urine  might  be  made  a  measure 
of  the  protein  destruction  in  the  body.1  Bidder  and  Schmidt2 
were  the  first  to  make  systematic  experiments  upon  this 
subject.  They  gave  meat  to  dogs  and  cats  and  found  that 
almost  all  the  nitrogen  contained  in  the  meat  was  eliminated 
in  the  urine  and  in  the  feces.  They3  make  the  following 
striking  statement,  which  rings  quite  true  to  modern  thought 
concerning  protein  metabolism:  "Almost  all  the  nitrogen  of 
protein  and  collagen  is  split  from  its  combination  and  carries 

1  Liebig:  ''Die  organische  Chemie  in  ihrer  Anwendung  auf  Physiologie 
und  Pathologie,"  1842. 

2  Bidder  and  Schmidt:  "Die  Verdauungssafte  und  der  Stoffwechsel," 
1852,  pp.  S33,  339- 

3  Bidder  and  Schmidt:  Ibid.,  p.  387. 


INTRODUCTORY  21 

with  it  enough  carbon,  hydrogen,  and  oxygen  to  form  urea; 
the  remaining  part,  containing  five-sixths  of  the  total  heat 
value  of  the  protein,  undergoes  oxidation  to  carbon  dioxid 
and  water  which  are  eliminated  in  the  respiration,  the  calori- 
facient  function  having  been  fulfilled."  The  results  obtained 
by  Bidder  and  Schmidt  were  attacked  and  were  not  finally 
established  until  proof  was  afforded  by  Carl  v.  Voit,1  who 
established  the  fact  that  an  animal  could  be  brought  into 
what  he  called  nitrogenous  equilibrium.  In  this  condition 
the  nitrogen  of  the  protein  eaten  was  equal  to  the  nitrogen 
eliminated  from  the  body  in  the  urine  and  feces.  Thus 
Voit2  fed  a  dog  for  fifty-eight  days  with  29  kilograms  of  meat 
containing  986  grams  of  nitrogen,  and  found  982.8  grams  of 
nitrogen  in  the  excreta  of  the  period.  The  amount  of  N  in 
the  urine  was  943.7  grams,  and  in  the  feces  39.1  grams.  The 
difference  between  the  amount  of  nitrogen  ingested  and  that 
recovered  in  the  excreta  was  only  T\  of  1  per  cent.  It 
therefore  seemed  extremely  probable  that  the  excretory  out- 
let for  protein  nitrogen  was  in  the  urine  and  in  the  feces 
and  that  other  sources  of  its  loss  were  normally  negligible. 
But  in  order  to  establish  the  fact  it  was  necessary  to  consider 
the  following  questions: 

Is  the  nitrogen  of  the  air  built  up  into  organic  compounds 
within  the  body?  Is  any  protein  nitrogen  given  off  as  nitrogen 
gas?  As  ammonia  gas?  In  the  sweat?  How  much  is  lost 
through  the  growth  of  the  hair,  nails,  and  epidermis? 

Lavoisier  had  said  that  nitrogen  gas  had  nothing  to  do 
with  respiration.  Regnault  and  Reiset3  sometimes  found 
that  animals  under  a  bell-jar  absorbed  nitrogen  gas  and  at 
other  times  gave  it  off.  The  quantity  in  both  cases  was 
extremely  small  and  can  be  explained  by  slight  errors  in  gas 
analysis  due  to  inexact  temperature  records.  Regnault  and 
Reiset  found  no  measurable   quantities  of  ammonia  or  of 

1Voit:   "Physiol.  Chem.  Untersuchungen,"  1857. 

2  Voit:    "Zeitschrift  fur  Biologie,"  1866,  ii,  35. 

3  Regnault  and  Reiset:  "An.  de  chiraie  et  phys.,"  Paris,  1849,  Sec.  3,  Tome 
xxvi. 


22  SCIENCE    OF    NUTRITION 

sulphur-containing  gases  in  the  expired  air,  and  they  dis- 
covered that  hydrogen  might  replace  nitrogen  in  the  atmos- 
phere without  affecting  the  course  of  metabolism. 

The  experiments  of  Bachl1  showed  that  a  rabbit  with  a 
tracheal  cannula  could  be  made  to  expire  for  six  hours  through 
Nessler's  reagent  without  the  indication  of  a  trace  of  ammonia 
in  the  breath.  This  has  also  been  shown  after  making  an 
Eck  fistula  in  a  dog,2  where  there  is  an  increase  in  the  amount 
of  ammonia  in  the  blood  and  in  the  urine.  The  lungs  are  not 
permeable  to  ammonia.3  The  ordinary  insensible  perspiration 
is  not  accompanied  by  any  appreciable  loss  of  nitrogenous 
excreta,  although  profuse  sweating  certainly  brings  out  some 
urea,  uric  acid,  and  other  nitrogen  extractives  normally 
excreted  in  the  urine.  The  experiments  of  Benedict4  show 
that  the  cutaneous  excretions  of  a  resting  man  may  amount 
to  0.071  gram  nitrogen  per  day;  of  a  man  at  moderate  work 
to  0.13  gram  per  hour,  and  at  hard  work  for  four  hours  to 
0.22  gram  per  hour. 

Voit5  collected  the  hair  and  epidermis  from  a  dog  for  565 
days  and  found  an  average  daily  output  of  1.2  grams  with 
0.18  gram  of  nitrogen.  Moleschott6  cut  the  hair  and  nails 
of  several  men  once  a  month.  The  daily  outgrowth  of  hair 
was  0.20  gram  with  0.029  gram  of  nitrogen,  and  of  nail  sub- 
stance 0.005  gram  with  0.0007  gram  of  nitrogen.  The  waste 
through  the  human  epidermis  has  not  been  measured,  but  it 
must  be  very  slight.  The  above  sources  of  error  were  thus 
shown  to  be  negligible. 

The  view  that  the  nitrogen  of  the  urine  and  feces  could 
be  made  a  measure  for  the  determination  of  protein  metabolism 
was  thus  securely  established.  Urea,  the  principal  nitrog- 
enous end-product  derived  from  protein,  was  therefore  shown 
to  be  not  an  adventitious  product,  but  one  normally  pro- 

1  Bachl:    "Zeitschrift  fur  Biologie,"  1869,  v,  61.  _ 

2Salaskin:   "Zeitschrift  fur  physiologische  Chemie,"  1898,  xxv,  463.^ 

3  Magnus:  "Archiv  fur  ex.  Pathologie  und  Pharmakologie,"  1902,  xlviii,  100. 

4  Benedict:   "Journal  of  Biological  Chemistry,"  1906,  i,  263. 
6  Voit:   "Zeitschrift  fur  Biologie,"  1866,  ii,  207. 

6 Moleschott:    "Untersuchungen  zur  Naturlehre,"  xii,  187. 


INTRODUCTORY  23 

portional  to  the  protein  destruction.  It  was  known  that 
meat  protein  in  general  contained  about  16  per  cent,  of 
nitrogen,  or  i  gram  of  nitrogen  in  6.25  grams  of  protein. 
Therefore  for  every  gram  of  nitrogen  found  in  the  excreta, 
6.25  grams  of  protein  have  been  destroyed  in  the  body.  It 
is  evident  that  if  protein  nitrogen  be  retained  in  the  body  a 
new  construction  of  body  tissue  is  indicated,  whereas  if  more 
nitrogen  is  eliminated  than  is  ingested  with  the  food,  a  waste 
of  body  tissue  must  take  place.  The  discovery  of  the  method 
of  calculating  the  protein  metabolism  led  Voit  to  suggest  to 
Pettenkofer  that  he  construct  an  apparatus  with  which  the 
total  carbon  excretion  might  be  measured,  including  that  of 
the  respiration  as  well  as  that  of  the  urine  and  the  feces. 
Voit  saw  that  with  these  data  it  would  be  possible  to  deter- 
mine just  how  much  of  each  food-stuff  was  actually  burned 
in  the  human  body.  He  has  described  the  delight  which  he 
and  Pettenkofer  experienced  when  their  wonderful  machine 
began  to  tell  its  tale  of  the  life  processes.  The  cost  of  the 
apparatus,  which  was  considerable,  was  defrayed  by  King 
Maximilian  II  of  Bavaria; 

It  has  been  stated  that  the  form  of  Lavoisier's  respiration 
apparatus  is  unknown.  In  1850  Regnault  and  Reiset1  pub- 
lished an  account  of  respiration  experiments  in  which  small 
animals  were  placed  under  a  bell-jar  containing  a  known 
quantity  of  oxygen.  The  air  was  kept  free  from  carbon 
dioxid  by  pumping  it  through  potassium  hydrate,  and  oxygen 
was  added  from  time  to  time.  The  gaseous  exchange  between 
the  animal  and  its  environment  could  be  readily  ascertained 
by  determining  the  amount  of  carbon  dioxid  given  off  and  the 
amount  of  oxvgen  absorbed.  No  attempt  was  made  to  de- 
termine from  what  materials  the  carbonic  acid  arose.  The 
method  of  Regnault  and  Reiset  placed  the  animals  in  a  con- 
fined space  where  poisonous  exhalations  other  than  carbon 
dioxid  could  collect,  and  where  the  atmosphere  became  satu- 
rated  with   water.     However,    these   factors   were   without 

1  Regnault  and  Reiset:  "An.  d.  Chem.  und  Pharm.,"  1850,  lxxiii,  92, 129,  257. 


24  SCIENCE    OF    NUTRITION 

influence  on  the  health  of  their  animals.  They  planned  to 
work  in  one  of  the  large  hospitals  in  Paris,  but,  unfortunately, 
the  project  proved  too  costly  and  had  to  be  renounced.  They 
write,  "L'etude  de  la  respiration  de  l'homme  dans  ses  divers 
etats  pathologiques  nous  parait  un  des  sujets  les  plus  dignes 
d'occuper  les  hommes  qui  se  vouent  a.  l'art  de  guerir:  elle 
peut  donner  un  diagnostic  precieux  pour  un  grand  nombre  de 
maladies  et  rendre  plus  evidentes  les  revolutions  qui  survien- 
nent  dans  l'economie."  Although  Regnault  and  Reiset  had 
no  definite  idea  of  the  materials  which  were  oxidized  in  the 
animals  with  which  they  were  experimenting,  we  find  that 
Bischoff  and  Voit1  tried  to  read  such  interpretations  into  the 
work  of  Regnault  and  Reiset.  Thus  Bischoff  and  Voit  de- 
termined the  quantity  of  nitrogen  in  the  urine  of  a  starving 
dog,  which  indicated  that  he  had  burned  in  twenty-four  hours 
218  grams  of  his  own  "flesh."  The  flesh  was  calculated  from 
the  nitrogen  elimination  on  the  basis  of  the  knowledge  that 
fresh  meat  contains  3.4  per  cent,  of  nitrogen.  Many  of  the 
older  experiments  were  computed  on  this  basis.  It  was  shown 
that  the  218  grams  of  "flesh"  contained  40  grams  of  carbon. 
Bischoff  and  Voit  estimate  from  the  experiments  of  Regnault 
and  Reiset  that  a  meat-fed  dog  of  a  weight  similar  to  the 
above  would  give  off  250  grams  of  carbon  and  absorb  900 
grams  of  oxygen  in  the  respiration  of  twenty-four  hours. 
These  figures  indicated  to  Bischoff  and  Voit  that  the  extra 
carbon  elimination  was  due  to  the  combustion  of  fat,  and  they 
reached  the  conclusion  that  the  waste  of  the  body  in  starvation 
is  dependent  on  the  metabolism  of  protein  and  fat.  Correct 
results,  however,  were  attainable  only  by  combining  the  two 
methods,  so  that  both  the  quantity  of  the  nitrogen  and  carbon 
of  the  urine  and  feces  and  the  amount  of  carbon  dioxid  of 
the  respiration  during  the  same  period  of  time  could  be  as- 
certained. This  was  accomplished  by  the  respiration  ap- 
paratus of  Pettenkofer. 

bischoff  and  Voit:     "Die  Gesetze  der  Ernahrung  des  Fleischfressers," 
i860,  p.  43. 


INTRODUCTORY  25 

The  problem  to  be  solved  by  Pettenkofer  included  the 
maintenance  of  a  man  in  normal  surroundings.  A  small  room 
was  therefore  constructed  which  was  well  ventilated  by  a 
current  of  air.  This  air  entered  the  chamber  freely  through 
an  opening  in  connection  with  a  large  room  outside  and  was 
aspirated  from  a  second  opening  in  the  chamber,  through  a 
large  gas-meter,  where  its  volume  was  measured  (500,000 
liters  per  day).  It  was  evidently  impracticable  to  determine 
all  the  carbon  dioxid  in  this  large  volume  of  air,  but  its  amount 
was  calculated  from  the  analysis  of  duplicate  samples  con- 
tinually withdrawn  from  the  air  leaving  the  chamber  during 
the  time  of  the  experiment.  Each  sample,  as  it  was  pumped 
out,  was  made  to  pass  over  calcined  pumice  stone  soaked  in 
sulphuric  acid,  to  remove  the  water.  Next  it  bubbled  through 
baryta  water  to  remove  the  carbon  dioxid,  and  then  passed 
through  a  small  gas-meter,  where  the  volume  of  the  sample 
was  measured.  After  this  fashion  the  amount  of  carbon 
dioxid  and  water  coming  from  the  air  of  the  chamber  was 
determined  in  duplicate.  Other  duplicate  analyses  of  the  air 
taken  outside  the  ventilator  just  before  it  entered  the  chamber 
were  simultaneously  made  in  the  same  manner  as  were  the 
analyses  of  the  chamber  air  itself.  Knowing  the  quantity 
of  carbon  dioxid  and  water  entering  and  leaving  the  room, 
it  was  easy  to  calculate  how  much  was  derived  from  the  man 
living  in  it  during  the  period  of  experimentation.  The 
experimenters  failed  to  find  any  other  gaseous  exhalation 
from  a  man,  such  as  ammonia,  hydrogen,  or  methane,  which 
could  vitiate  their  results.  Control  experiments  were  made 
by  burning  a  candle  or  evaporating  a  known  weight  of  water 
within  the  room.  Analysis  showed  that  the  carbon  dioxid 
and  water  so  produced  were  measurable  within  1  per  cent, 
of  error. 

As  an  illustration  of  the  practical  working  of  the  respira- 
tion apparatus  the  first  experiment  of  Pettenkofer  and  Voit,1 
which  gives  the  metabolism  in  a  starving  man,  will  be  described. 

1  Pettenkofer  and  Voit:   "Zeitschrift  fur  Biologie,"  1866,  ii,  478. 


26  SCIENCE    OF    NUTRITION 

The  man  was  allowed  a  small  quantity  of  Liebig's  extract 
of  beef,  as  the  experimenters  did  not  at  that  time  realize 
the  very  slight  discomfort  usually  entailed  by  total  ab- 
stinence from  food.  As  Liebig's  extract  has  no  nutritive 
value,  its  effect  has  been  counted  out  in  the  following 
description. 

The  subject,  on  entering  the  living-room  of  the  apparatus, 
weighed  71.090  kilograms,  and  he  drank  during  the  day  1.0548 
liters  of  water,  making  a  total  body  weight  of  72.1448  kilo- 
grams. Twenty-four  hours  later  he  weighed  70.160  kilo- 
grams and  his  excreta  had  amounted  to  0.7383  kilogram 
carbon  dioxid,  0.8289  kilogram  water  from  lungs  and  skin,  and 
1. 1975  kilograms  of  urine.  The  final  body  weight  plus  all 
the.  excreta  amounted  to  72.9247  kilograms.  A  total  body 
weight  of  72.1448  kilograms  was  converted  into  a  body  weight 
plus  excreta  amounting  to  72.9247  kilograms.  The  difference 
is  due  to  oxygen  absorbed.  The  difference  of  0.7799  kilogram 
represents  the  amount  of  oxygen  needed  to  convert  the  body 
substance  lost  into  the  excretory  products  obtained.  The 
tabular  statement  reads: 

MAN— STARVATION 

Kg.  Kg. 

Weight  at  start 71.090  Weight  at  end 70.160 

Water  drunk 1-0548  Carbon  dioxid 0.7383 

Water  in  respiration 0.8289 

Oxygen  absorbed 0.7799  Urine ^--^IS 


72.9247  72.9247 

The  analysis  of  the  urine  showed  12.51  grams  of  nitrogen 
and  8.25  grams  of  carbon.  A  calculation  gives  the  amount  of 
carbon  in  the  respiration  as  201.3  grams.  If  we  neglect  the 
feces  as  being  too  small  in  starvation  to  influence  the  results, 
we  find  that  the  total  carbon  elimination  for  twenty-four  hours 
was  209.55  grams,  and  the  total  nitrogen  12.51.  In  the 
Liebig  extract  ingested  there  were  2.44  grams  of  carbon  and 
1. 1 8  grams  of  nitrogen,  which  must  be  deducted  from  the 
above  in  order  to  obtain  the  strict  loss  of  carbon  and  nitrogen 


INTRODUCTORY 


27 


from  the  body  during  the  period  of  starvation.  These 
values  are: 

C 207.11  grams. 

N 11.33      " 

These  two  figures  enabled  Pettenkofer  and  Voit  to  cal- 
culate what  substances  had  burned  in  the  body.  As  every 
gram  of  nitrogen  in  the  excreta  is  approximately  represented 
by  the  destruction  of  6.25  grams  of  meat  protein,  the  amount 
of  such  protein  destroyed  by  the  man  was  70.81  grams.  It 
has  been  found  that  for  every  gram  of  nitrogen  present  in 
meat  protein  there  are  3.28  grams  of  carbon.  It  is  therefore 
easy  to  estimate  that  destruction  of  protein  represented  by 
11.33  grams  of  nitrogen  involved  the  elimination  of  37.16 
grams  of  carbon.  Now,  the  man  eliminated  207.11  grams  of 
total  carbon,  from  which  this  protein  carbon  may  be  deducted, 
leaving  as  residue  169.95  grams,  which  must  have  originated 
from  a  source  other  than  protein.  The  possible  sources  are 
two  in  number — carbohydrates  and  fats.  In  starvation  no 
carbohydrates  are  ingested  and  their  supply  in  the  form  of 
reserve  glycogen  is  usually  counted  as  being  negligible  in 
such  experiments  as  these.  The  only  other  source  from  which 
the  169.95  grams  of  extra  carbon  could  have  been  derived  is 
fat,  and  as  fat  contains  76.52  per  cent,  of  carbon,  a  destruction 
of  222.1  grams  of  fat  may  be  calculated.  This  fasting  man 
therefore  destroyed: 

Protein 70.81  grams. 

Fat 222.1        " 

That  such  metabolism  actually  did  take  place  was  further 
indicated  by  the  comparison  of  the  amount  of  oxygen  needed 
for  the  destruction  of  the  above  constituents,  and  the  amount 
of  oxygen  absorption  as  determined  by  the  experiment. 

From  the  constituents  of  the  protein  and  fat  destroyed, 
Pettenkofer  and  Voit  deducted  the  constituents  of  the  urine, 
which  contains  part  of  the  C  and  H  belonging  to  protein. 
The  balance  of  the  carbon  and  hydrogen  was  fit  for  oxidation 


28  SCIENCE   OF   NUTRITION 

to  carbon  dioxid  and  water.     Their  calculation  may  thus  be 
presented : 

Weight  in  Grams. 
C  HO 

Composition  of  the  protein  burned 37-i6  5.8         17. 1 

Composition  of  fat  burned 169.95  25.7         25.1 


Total  C,  H,  and  O  metabolized 207.11  31.5         42.2 

Deduct  quantity  in  the  urine 8.2  2.0  7.6 


Balance  available  for  respiratory  CO2  and  H2O 198.9             29.5  34.6 

Oxygen  required 530.4  235.7 

Total  O  required  for  the  formation  of  CO2  and  H2O 766.1 

Less  O  in  the  protein  and  fat 34.6 

Oxygen  actually  required 73* -5 

Oxygen  absorption  as  determined 779-9 


Difference 48.4 

We  may  reach  the  same  result  by  using  the  most  modern 
figures  for  the  oxygen  requirement  in  the  metabolism  of  the 
food-stuffs.  We  now  know  that  to  burn  100  grams  of  meat 
protein  requires  13343  grams  of  oxygen,  and  to  burn  100  grams 
of  fat  requires  288.5  grams,  and  to  burn  100  grams  of  starch 
1 18.5  grams.     This  being  true,  there  are  required: 

Oxygen. 

For  70. Si  grams  protein 94-44  gm. 

For  222.1  grams  fat 639.55  gm- 


Total  required 733-99  gm- 

Oxygen  absorption  as  found 779-9     gm. 


Difference 45-91  gm. 

Had  carbohydrates  burned,  less  oxygen  would  have  been 
needed,  since  carbohydrates  contain  a  larger  proportion  of 
oxygen  than  fats.  Had  the  extra  169.95  grams  of  carbon  been 
due  to  the  combustion  of  starch  (or  glycogen),  382  grams 
would  have  burned,  requiring  452.7  grams  of  oxygen  instead 
of  639.5  grams  for  fat.  Pettenkofer  and  Voit  found  in  the 
amount  of  oxygen  absorption  a  confirmation  of  their  belief 
that  the  fasting  organism  supports  itself  by  the  combustion 
of  its  own  protein  and  fat. 

It  is  apparent  from  this  discussion  that  the  quantity  of  oxygen 
needed  in  metabolism  depends  upon  the  chemical  composition  of  the 


INTRODUCTORY  29 

material  that  bums  in  the  organism,  and  also  that  the  relation 
between  the  amount  of  oxygen  absorbed  and  carbon  dioxid 
excreted  depends  on  the  same  factor.  Regnault  and  Reiset  fre- 
quently observed  that  this  latter  relationship  was  variable.  The 
ratio  of  the  volume  of  carbon  dioxid  expired  to  the  volume  of 
oxygen  inspired  during  the  same  time  is  called  the  respiratory 
quotient  (see  p.  57).  When  carbohydrates  burn,  the  R.  Q.  is 
unity;  that  is,  for  every  hundred  volumes  of  carbon  dioxid 
excreted  a  hundred  volumes  of  oxygen  are  absorbed.  When 
protein  burns  the  quotient  is  \0^  q°*  =  —  or  0.781,  and  when 
fat  burns  the  quotient  is  0.71.  Pettenkofer  and  Voit  cal- 
culated that  the  respiratory  quotient  in  their  fasting  man  was 
0.69.     This  indicated  a  combustion  of  fat  in  the  organism. 

The  further  researches  of  Pettenkofer  and  Voit  were 
founded  on  the  principles  described  in  the  above  experiment 
on  a  fasting  man.  If  meat  and  fat  were  ingested,  the  carbon 
and  nitrogen  excreta  were  collected,  and  from  these  data  it 
was  determined  how  much  of  each  food-stuff  was  oxidized  and 
whether  there  was  a  storage  of  either  in  the  body  or  a  loss  of 
either  from  the  body.  If  a  mixed  diet  which  included  carbo- 
hydrates were  given,  the  carbon  dioxid  elimination  increased 
and  the  oxygen  absorption  was  such  as  indicated  the  com- 
bustion of  carbohydrates.  It  was  assumed  that  after  deduct- 
ing the  protein  carbon  from  the  total  carbon  eliminated,  the 
balance  of  extra  carbon  was  derived  from  the  destruction  of 
the  carbohydrates  in  so  far  as  these  were  ingested;  any  carbon 
in  excess  of  this  was  attributed  to  fat  combustion. 

Voit,1  in  his  necrology  of  Pettenkofer,  writes:  "Imagine  our 
sensations  as  the  picture  of  the  remarkable  processes  of  the 
metabolism  unrolled  before  our  eyes,  and  a  mass  of  new  facts 
became  known  to  us!  We  found  that  in  starvation  protein 
and  fat  alone  were  burned,  that  during  work  more  fat  was 
burned,  and  that  less  fat  was  consumed  during  rest,  especially 
during  sleep ;  that  the  carnivorous  dog  could  maintain  himself 
on  an  exclusive  protein  diet,  and  if  to  such  a  protein  diet  fat 

1  Voit:   "Zeitschrift  fur  Biologie,"  1901,  x!i,  1. 


3<D  SCIENCE    OF   NUTRITION 

were  added,  the  fat  was  almost  entirely  deposited  in  the  body; 
that  carbohydrates,  on  the  contrary,  were  burned  no  matter 
how  much  was  given,  and  that  they,  like  the  fat  of  the  food, 
protected  the  body  from  fat  loss,  although  more  carbohydrates 
than  fat  had  to  be  given  to  effect  this  purpose;  that  the  metab- 
olism in  the  body  was  not  proportional  to  the  combustibility 
of  the  substances  outside  the  body,  but  that  protein,  which 
burns  with  difficulty  outside,  metabolizes  with  the  greatest 
ease,  then  carbohydrates,  while  fat,  which  readily  burns 
outside,  is  the  most  difficultly  combustible  in  the  organism." 

Since  the  days  of  these  researches  repeated  experiments 
have  established  the  verity  of  the  conclusions  drawn.  It  is 
interesting  to  note  that  among  the  earliest  experiments  made 
were  some  upon  patients  in  pathologic  conditions,  one  suf- 
fering from  leukemia,  another  from  diabetes. 

Besides  the  influence  of  foods  upon  metabolism,  the  changes 
brought  about  by  exercise,  temperature,  and  drugs  were  in- 
vestigated not  only  by  the  Munich  school,  but  by  many  other 
workers.  Similar  investigations  are  actively  progressing  to- 
day. 

Among  the  important  conclusions  -reached  by  Voit  was 
that  concerning  the  manner  of  the  metabolism.  It  has  been 
stated  that  Liebig  believed  that  fat  and  carbohydrates  were 
destroyed  by  oxygen,  while  protein  metabolism  took  place  on 
account  of  muscle  work. 

Voit1  showed  that  muscle  work  did  not  increase  protein 
metabolism  and  that  the  metabolism  was  not  proportional  to  the 
oxygen  supply.  The  oxygen  absorption  apparently  depended . 
upon  what  metabolized  in  the  cells.  Voit  believed  that  the 
cause  of  metabolism  was  unknown,  that  the  process  was  one 
of  cleavage  of  the  food  molecules  into  simpler  products, 
which  could  then  unite  with  oxygen.  Yeast  cells,  for  example, 
convert  sugar  into  carbonic  acid  and  alcohol  without  the 
intervention  of  oxygen.  In  like  manner  the  first  products  of 
the  decomposition  of  fat,  sugar,  and  protein  are  formed  in 

1  Voit:   "Zeitschrift  fur  Biologie,"  1866,  ii,  535. 


INTRODUCTORY 


31 


metabolism  through  unknown  causes.  Some  of  these  pre- 
liminary decomposition  substances  may  unite  with  oxygen  to 
form  carbon  dioxid  and  water,  others  may  be  converted  into 
urea,  while  others  under  given  circumstances  may  be  syn- 
thesized to  higher  compounds.  In  any  case  the  absorption  of 
oxygen  does  not  cause  metabolism,  but  rather  the  amount  of  the 
metabolism  determines  the  amount  of  oxygen  to  be  absorbed  (see 

P-32)- 

The  statement  is  frequently  met  with  in  the  literature  of 

the  subject  that  such  and  such  a  disease  is  the  consequence  of 

deficient  oxidative  power  in  the  tissues.     For  example,  it  has 

been  stated  that  alcohol  decreases  the  oxidative  power  of  the 

liver  for  uric  acid.1     Such  apparent  decrease  in  oxidative 

power  may,  however,  be  due  to  the  fact  that  the  normal 

oxidizable  cleavage  products  are  not  formed  and,  therefore,  no 

oxidation  can  take  place.     It  is  not  due  to  lack  of  oxygen  that 

sugar  is  not  oxidized  in  diabetes,  or  cystin  in  cystinuria. 

There  is  the  normal  supply  of  oxygen  present,  but  the  cleavage 

of  these  substances  into  bodies  which  can  unite  with  oxygen 

cannot  be  effected,  and  hence  they  cannot  be  metabolized. 

Voit's  pupil,  Lossen,2  showed  that  the  carbon  dioxid 
elimination  in  respiration  was  independent  of  the  ventilation 
of  the  lungs  except  in  so  far  as  forced  breathing  increased  the 
muscular  work  and  the  consequent  output  of  carbon  dioxid. 

When  the  depth  of  respiration  was  voluntary  the  results 
were  as  follows: 


Number  of  Res- 
pirations  per 
Minute. 

Volume  of  Expired 
Air  in  15  Minutes. 

Volume  of  One  Respi- 
ration. 

CO2  in  15  Minutes. 

Liters. 

C.C 

Grams. 

5 

75-i 

1002 

7.96 

10 

83.6 

558 

7-44 

IS 

94-4 

420 

7-32 

20 

120.3 

401 

8.14 

3° 

121. 0 

269 

7.18 

40 

I38-5 

231 

6.76 

60 

182.7 

203 

6.63 

1  Beebe,  S.  P.:   "American  Journal  of  Physiology,"  1904,  xii,  36. 

2  Lossen:   "Zeitschrift  fur  Biologie,"  1866,  ii,  244;  1870,  vi,  298. 


32  SCIENCE    OF   NUTRITION 

Pfluger,1  who  through  different  reasoning  came  to  the  same 
conclusion  as  Voit,  devised  an  experiment  in  which  a  rabbit 
breathed  quietly  through  a  cannula,  and  the  oxygen  absorption 
was  compared  with  that  of  the  same  animal  when  rapid  arti- 
ficial ventilation  of  the  lungs  with  air  took  place,  producing 
apnea  or  hyperarterialization  of  the  blood.  There  was  no 
difference,  as  is  seen  from  the  following  table: 


Series  I . . 
Series  II. 


Oxygen  Absorbed  in  CC.  During  15  Minutes. 


Normal  respiration. 


201.66 
203.21 


Apnea. 


203.88 
210.47 


From  these  experiments  it  is  made  sure  that  the  respiration 
does  not  cause  or  regulate  metabolism.  On  the  contrary,  the 
metabolism  regulates  the  respiration.  The  metabolism  of  the 
tissues,  through  its  oxygen  requirement  and  its  carbon  dioxid 
production,  changes  the  condition  of  the  blood  and  thereby  regu- 
lates the  respiration.  These  distinctions  are  of  fundamental 
importance. 

Thus  far  the  history  of  the  principles  which  underlie  the 
exact  measurement  of  the  metabolism  has  been  briefly  given. 
By  metabolism  is  meant  the  chemical  changes  of  materials  under 
the  influence  of  living  cells.  The  first  cause  of  these  chem- 
ical changes,  it  has  been  seen,  is  unknown,  but  their  results 
lead  to  motions  of  the  smallest  component  parts  of  protoplasm, 
motions  whose  totality  we  call  life.  Phenomena  of  life  are 
phenomena  of  motion  due  to  liberation  of  energy  in  the  break- 
ing down  of  molecules.  The  motions  are  principally  mani- 
fested as  heat,  mechanical  energy,  and  electric  currents.  In 
the  organism  mechanical  energy  may  be  converted  into  heat, 
as  appears  when  work  of  the  heart  is  converted  into  heat 
by  the  friction  of  the  blood  upon  the  capillaries.  Also  the 
current  of  electricity  developed  at  each  systole  of  the  heart,  or 
in  any  other  active  tissue,  is  resolved  into  heat.     Thus  heat 

1  Pfluger:   "Archiv  fur  die  ges.  Physiologie/'  1877,  xiv,  1. 


INTRODUCTORY  33 

may  become  a  measure  of  the  total  activity  of  the  body.  It  is 
derived  from  the  total  metabolism  and  must  be  dependent  on 
it  and  be  a  measure  of  it.  Hence  the  physical  activities 
noted  in  life  are  the  results  of  chemical  decompositions. 
Metabolism  vivifies  the  energy  potential  in  chemical  com- 
pounds. 

Lavoisier1  was  the  first  to  recognize  that  animal  heat  was 
derived  from  the  oxidation  of  the  body's  substance  and  to 
compare  animal  heat  to  that  produced  by  a  candle.  To 
prove  this  he  burned  a  known  quantity  of  carbon  in  an  ice- 
chamber  and  noted  the  amount  of  ice  melted.  He  then 
calculated  the  amount  of  heat  produced  from  a  unit  of  carbon. 
He  and  Laplace  put  a  guinea-pig  in  an  ice-chamber  and  noted 
the  amount  of  ice  which  melted  during  ten  hours  and  calculated 
the  heat  given  off  from  the  animal.  They  then  determined 
how  much  carbon  dioxid  the  guinea-pig  gave  off.  The  animal 
yielded  31.82  calories  to  the  ice-chamber,  while  a  calculation 
from  the  respiratory  analysis  showed  that  25.408  calories 
could  have  been  derived  by  the  burning  of  enough  carbon  to 
yield  the  same  amount  of  carbon  dioxid  as  was  eliminated  by 
the  animal. 

Lavoisier  realized  several  of  the  errors  in  his  work.  For 
example,  the  calorimetric  determination  on  the  animal  was 
made  at  a  different  temperature  from  that  of  the  respiratory 
experiment,  and  Lavoisier  knew  that  cold  would  raise  the 
carbon  dioxid  output.  Also  cold  reduced  the  heat  in  the 
animal  itself,  and,  further,  the  water  of  respiration  was  added 
to  that  of  the  melting  ice.  But  Lavoisier  concluded  that  the 
source  of  the  heat  lay  in  the  oxidation  of  the  body. 

Crawford,  in  England  in  1777,  found  after  burning  wax  and 

carbon,  or  on  leaving  a  live  guinea-pig  in  his  water  calorimeter, 

that  for  every  100  ounces  of  oxygen  used  the  water  was  raised 

the  following  number  of  degrees  Fahrenheit : 

Wax 2.1 

Carbon 1 .93 

Guinea-pig 1.73 

1  Lavoisier  and  Laplace:  Academie  des  Sciences,  1780,  p.  379. 

3 


34  SCIENCE    OF   NUTRITION 

Crawford  concluded  that  the  heat  above  produced  was  due  to 
the  transformation  of  pure  air  into  fixed  air  (carbon  dioxid) 
and  water. 

The  methods  of  Crawford,  though  primitive,  were  based 
on  fundamental  principles,  for  according  to  the  modern  com- 
putation of  Zuntz  the  values  of  heat  production  where  i  liter 
of  oxygen  is  used  to  burn  the  different  food-stuffs  in  the  body 
are  very  nearly  identical  (see  p.  62). 

In  1823  the  French  Academy  awarded  a  prize  for  the 
best  essay  on  the  subject  of  animal  heat.  Depretz  and 
Dulong  competed  for  the  prize  and  it  was  awarded  to  the 
former.    * 

Depretz1  calculated  the  amount  of  heat  which  would  have 
been  liberated  in  burning  the  carbon  and  hydrogen  of  the 
metabolism  to  carbon  dioxid  and  water,  and  compared  this 
with  the  amount  of  heat  given  off  by  the  animal.  The  heat  as 
calculated  was  only  74  to  90  per  cent,  of  what  was  found,  a 
discrepancy  due  to  faults  in  the  method  employed  (see  p.  43). 
So  Depretz  concluded  that  although  the  respiration  was  the 
principal  source  of  animal  heat,  food,  the  motion  of  the  blood, 
and  friction  yielded  the  remainder.  Interpretation  along  the 
lines  of  the  law  of  the  conservation  of  energy  was  obviously 
beyond  the  ideas  of  the  time. 

Dulong's2  experiments  also  led  to  the  same  conclusion, 
that  oxidation  was  insufficient  to  explain  the  cause  of  animal 
heat,  and  that  there  must  be  other  sources  of  it. 

Regnault  and  Reiset,  writing  in  1849  regarding  the  com- 
putation of  heat  production  from  the  oxygen  absorbed  by  an 
animal,  remark,  "The  phenomena  are  evidently  so  complex 
that  it  is  scarcely  probable  that  one  will  ever  be  able  to 
submit  them  to  calculation." 

About  1842  James  P.  Joule  supplied  the  chief  experimental 
data  which  established  the  mechanical  equivalent  of  heat. 
In  1845  J.  R.  Mayer  laid  down  the  law  of  the  conservation 

1  Depretz:  "Journal  de  Physiologie,"  1824,  iv,  143. 

2  Dulong:  Ibid.,  1823,  iii,  45. 


INTRODUCTORY  35 

of  energy,  and  in  1847  Helmholtz  independently  made  the 
same  discovery.  Both  contributions  were  rejected  by  the 
leading  German  scientific  journal  of  the  day.1  This  should 
encourage  all  workers  to  rest  assured  of  the  ultimate  recogni- 
tion of  work  that  is  worth  while. 

Energy  cannot  arise  from  nothing,  nor  can  energy  disappear 
into  nothing.  Where  energy  is  active  it  must  have  been 
elsewhere  potential.  The  sum  total  of  energy  remains  con- 
stant in  the  universe,  but  energy  may  vary  in  kind.  The 
kinds  include  mechanical  energy,  heat,  electricity,  magnetism, 
and  potential  energy.  The  source  of  energy  on  the  earth  is 
the  sun,  excepting  the  energy  of  the  tides,  which  is  due  princi- 
pally to  the  moon.  The  sun  unevenly  warms  the  atmosphere, 
producing  winds  which  drive  ships  and  windmills.  The  sun's 
heat  lifts  the  vapor  of  water  into  the  atmosphere,  producing 
rain,  in  consequence  of  which  rivers  are  made  to  turn  machin- 
ery. The  sunlight  acts  upon  a  mixture  of  hydrogen  and 
chlorin  gas,  causing  them  to  unite  with  a  loud  explosion,  and 
the  sun  acts  upon  the  green  leaf  of  the  plant,  causing  it  to 
unite  carbon  dioxid  and  water,  with  the  production  of  formic 
aldehyd,  which  is  built  up  into  sugar,  oxygen  being  given  off 
in  the  process.  The  sun's  energy  required  to  build  up  the  com- 
pound becomes  latent  or  potential  in  it.  Whenever  and 
wherever  this  sugar  is  again  converted  into  carbon  dioxid  and 
water  by  oxidation,  exactly  the  same  quantity  of  energy 
taken  from  the  sun  and  made  potential  in  the  sugar  is  set  free. 
This  sugar  in.  the  plant  may  be  further  converted  into  starch, 
cellulose,  fat,  and  possibly  into  protein.  Plants  furnish  wood 
and  coal  as  fuel  for  the  steam-engine.  They  also  furnish  the 
basis  of  animal  food,  yielding  substances  which  can  build 
up  animal  tissues,  and  which  can  furnish  the  energy  neces- 
sary to  maintain  those  motions  in  the  cells  whose  aggregate 
is  called  life.  These  motions  appear  in  the  body  as  heat, 
mechanical  work,  and  electric  currents,  all  of  which  may  be 
measured  as  heat.     Is  this  energy  completely  derived  from 

1  "Wiener  klin.  Wochenschr.,"  S.  Exner,  1914,  xxvii,  1529. 


36  SCIENCE    OF   NUTRITION 

the  metabolism?  This  question  is  but  the  continuation  of  the 
old  one  of  Lavoisier  in  the  light  of  newer  science. 

Bischoff  and  Voit1  in  i860  still  calculated  the  heat  value  of 
the  metabolism  from  the  heat  developed  in  burning  the  carbon 
and  hydrogen  elements  of  the  metabolism.  They  recognized, 
as  had  Bidder  and  Schmidt2  before  them,  that  this  was  a 
false  method,  and  stated  that  they  should  employ  the  calorific 
value  of  fat,  starch,  and  protein,  less  the  urea,  since  they 
recognized  that  urea  was  capable  of  undergoing  combustion 
with  liberation  of  heat. 

In  i860  Voit3  took  a  Thomson  calorimeter  with  him  from 
London  to  Munich.  After  Frankland's  determination  of  the 
heat  value  of  the  various  food-stuffs  and  urea  Voit4  prepared  a 
table  in  1866  for  use  in  his  lectures  showing  that  the  metab- 
olism of  the  fasting  man  experimented  on  by  Pettenkofer  and 
Voit  indicated  the  production  of  2.25  million  small  calories, 
while  the  metabolism  on  a  medium  diet  was  2.40  million 
calories. 

In  1873  Pettenkofer  and  Voit5  calculated  that  100  grams 
of  fat  were  the  physiologic  equivalent  of  175  grams  of 
starch.  Liebig  at  that  time  had  suggested  that  the  amount  of 
these  substances  which  could  be  burned  by  a  man  was  pro- 
portional to  the  oxygen  supply. 

Voit,  not  content  with  his  results,  suggested  to  Schurmann 
in  1878-79  that  he  carry  on  experiments  to  see  in  what  way 
carbohydrates  and  fat  were  interchangeable  in  nutrition. 
Schurmann  died  before  the  work  was  completed  and  the 
investigation  was  continued  by  Rubner.  The  isodynamic 
law,  which  showed  that  the  food-stuff s  may  under  given  conditions 
replace  each  other  in  accordance  with  their  heat- producing  value, 
was  the  result. 


1  Bischoff  and  Voit:     "Die  Gesetze  der  Ernahrung  des  Fleischfressers," 
i860,  p.  43. 

2  Bidder  and  Schmidt:    "Verdauungssafte  und  Stoffwechsel,"  1852,  p.  353. 

3  Voit:   "Munchener  medizinische  Wochenschrift,"  1902,  xlix,  233. 

4  Voit:  Ibid. 

5  Pettenkofer  and  Voit:   "Zeitschrift  fur  Biologie,"  1873,  ix,  534. 


INTRODUCTORY  37 

Rubner  gives  the  following  as  the  quantities  of  the  differ- 
ent food-stuffs  which  are  isodynamic: 

ioo  gm.  fat. 

232  gm.  starch. 

234  gm.  cane-sugar. 

243  gm.  dried  meat. 
After  Stohmann1  published  his  research  on  the  calorific 
value  of  foods,  urea,  etc.,  Voit  commenced  the  construction  of 
a  calorimeter  for  the  measurement  of  the  heat  eliminated 
from  the  body  of  a  man  whose  metabolism  was  simultaneously- 
determined.  The  results  obtained  by  the  use  of  this  machine 
were  never  published. 

Rubner2  in  Voit's  laboratory  during  this  same  period  was 
making  a  series  of  valuable  calorimetric  determinations.  The 
heat  value  to  the  body  of  burning  starch  and  fat  were  obviously 
the  same  as  that  determined  in  the  calorimeter,  since  in  both 
cases  the  same  end-products,  carbon  dioxid  and  water,  resulted. 
The  heat  value  of  protein  in  the  calorimeter  was  different  from 
its  fuel  value  to  the  body,  since  the  end-products  were  different 
in  the  two  cases.  When  protein  is  oxidized  in  the  body  the 
products  of  its  metabolism  are  lost  in  three  different  ways — 
through  the  respiration,  urine,  and  feces.  The  two  last  contain 
latent  heat  lost  to  the  body,  which  must  be  deducted  from  the 
heat  value  of  protein  determined  calorimetrically. 

The  custom  of  Stohmann  and  previous  authorities  had 
been  to  deduct  the  heat  value  of  urea  from  the  heat  value  of 
protein  in  order  to  obtain  the  actual  physiologic  or  fuel 
value  of  protein  for  the  organism.  But  in  the  earliest  ex- 
periments of  Pettenkofer  and  Voit3  it  was  recognized  that  in 
starvation  and  after  the  ingestion  of  meat  there  was  a  much 
larger  output  of  carbon  in  the  urine  than  corresponded  to  the 
quantity  of  urea  present.  The  ratio  of  nitrogen  to  carbon 
was  nearly  constant  in  the  urine  when  the  conditions  of  feeding 

1  Stohmann:  "Journal  fur  praktische  Chemie,"  1885,  xxxi,  273,  and  earlier 
papers. 

2  Rubner:    "Zeitschrift  fur  Biologie,"  1885,  xxi,  250,  337. 

3  Pettenkofer  and  Voit:   Ibid.,  1866,  ii,  471. 


38 


SCIENCE    OF    NUTRITION 


were  similar.  If  urea  alone  were  present,  Rubner  estimated 
there  would  be  0.429  gram  of  C  to  1  of  N  or  an  N  :  C  =  1  : 0.429. 
In  starvation  the  urine  contains  extractive  nitrogen  (creatinin, 
uric  acid,  etc.,  having  relatively  more  carbon  than  urea)  which 
has  been  derived  from  the  breaking  down  of  tissue  protein, 
and  the  ratio  isN:C=^i:o.728.  When  meat  was  ingested 
the  fact  that  the  food  contained  these  extractives  made  the 
C  :  N  ratio  0.610.  And  even  after  six  days'  ingestion  of  meat 
washed  free  from  extractives  the  urine  of  the  seventh  and 
eighth  days  still  showed  an  elimination  of  carbon  other  than 
that  due  to  urea,  as  was  indicated  by  the  ratio  0.532.  There- 
fore, from  the  metabolism  following  the  ingestion  of  the 
proteins  of  washed  meat  small  amounts  of  carbon  compounds 
other  than  urea  are  eliminated  in  the  urine. 

Rubner  saw  that  it  was  the  heat  value  of  the  urinary 
constituents  themselves  which  had  to  be  subtracted  from  the 
heat  value  of  protein  if  the  fuel  value  of  protein  to  the  body 
was  to  be  determined. 

The  following  table  shows  Rubner's  results  after  burning 
the  dry  urine : 

CALORIFIC  VALUE  OF  URINE 


Material  Burned. 

C:N. 

Calories 
from  1  Gram. 

Calorific  Value 
of  1  Gram  N. 

Urea 

0.429 

0-532 
0.610 
0.728 

2-523 
2.706 

2-954 
3.101 

5-41 
5-69 
7.46 

8.49 

Urine  after  feeding  protein 

Urine  after  feeding  meat 

Urine  in  starvation 

Benedict  and  Milner1  report  that  the  average  C  :  N  ratio 
in  man  when  he  partakes  of  a  mixed  diet  is  0.75  and  the 
calorific  value  of  a  gram  of  urinary  nitrogen  is  8.09.  When 
a  diet  which  is  high  in  carbohydrate  is  ingested  the  value  of  a 
gram  of  urinary  nitrogen  may  be  from  11  to  13  calories,2 

1  Benedict  and  Milner:  United  States  Dept.  of  Agriculture,  Office  of  Experi- 
ment Stations,  1907,  Bulletin  175,  p.  144. 

2Tangl.    "Archiv  fur  Physiologie,"  1899,  Supplement  Bd.,  p.  251. 


INTRODUCTORY  39 

an  increase  which  is  due  to  the  appearance  of  products  of  the 
intermediary  metabolism  of  glucose  (see  p.  208),  although 
no  glucose  itself  is  present.1 

It  was  not  alone  necessary  to  know  the  heat  value  of  the 
urine  excreted,  but  also  that  of  the  feces.  Rubner  found  that 
after  giving  100  parts  of  dry  muscle  containing  5.5  grams  of 
ash  there  was  an  elimination  of  38.2  grams  of  the  organic 
part  in  the  urine  and  2.7  grams  in  the  feces.  The  following 
table  represents  this  division  of  material  in  the  excreta: 

C               H.  N.  O. 

Composition  of  100  parts  dry  muscle 50.5  7.6  15.4  20.97 

Urine  contains  38.2  parts 9.63  2.52  15.16  10.9 

Feces  contain  2.7  parts 1.67  0.25  0.24  0.54 

Excreted  in  urine  and  feces 11.30         2.77         15.40         n.44 

Balance  for  respiration 39.2  4.8  9.53 

Rubner  determined  the  amount  of  heat  produced  from  i 
gram  of  ash-free  feces  after  meat  ingestion  and  found  it  to  be 
6.127  calories,  while  i  gram  of  ash-free  feces  after  protein 
(washed  meat)  ingestion  yielded  6.852  calories.  The  total 
calorific  value  of  1  gram  of  beef  muscle  when  Rubner  burned 
it  in  the  calorimeter  was  5.345  calories.  He  had  now  the 
principal  data  required  to  determine  its  heat  value  in  the  body. 
If  from  100  grams  of  meat  2.7  grams  appear  as  feces  having  a 
calorific  value  of  6.127  calories  per  gram,  then  there  is  here  a 
loss  of  6.127  X  2.7  =  16.83  calories.  If  from  every  100  grams 
of  meat  containing  15.4  grams  of  nitrogen  15.16  grams  of  the 
latter  appear  in  the  urine  and  such  urine  produced  by  ingesting 
meat  has  a  calorific  value  of  7.46  calories  for  every  gram  of 
nitrogen  present,  then  the  energy  loss  in  the  urine  would  be 
7.46  X  15.16  =  112.94  calories.  For  dry  muscle  substance 
we  find  therefore: 

Calories. 
100  grams  muscle 534-5 

^{?S::v:::::::::  *ag}-«- «*» 

Fuel  value  of  100  grams  of  dry  muscle 404.73 

1  Reale:    "Biochemische  Zeitschrift,"  1913,  lvii,  143. 


4° 


SCIENCE    OF   NUTRITION 


From  this  value  there  must  be  a  slight  deduction  for  the  heat 
present  in  the  protein  in  its  colloidal  state  but  lost  on  drying, 
and  for  the  heat  of  solution  necessary  to  dissolve  urea  and 
other  urinary  constituents.     Rubner  estimates  these  as: 

Heat  for  the  imbibition  of  protein 2.688 

Heat  for  solution  of  urea 1.989 


4.677 


Subtracting  4.67  from  404.73  leaves  400.06  calories  as  the 
maximum  of  energy  obtainable  from  100  grams  of  the  dried 
solids  of  meat.  The  calorimeter  shows  a  heat  value  of  534.5 
calories  for  the  same  protein.  Of  this,  400.06  calories,  or 
74.9  per  cent.,  are  available  in  the  organism,  while  the  re- 
mainder, or  25  per  cent.,  goes  to  waste. 

A  further  calculation  shows  that  every  gram  of  nitrogen  in 
the  urine  and  feces  represents  an  elimination  of  heat  from 
protein  metabolism  equal  to  25.98  calories.  The  heat  value 
of  protein  under  the  different  physiologic  conditions  was 
estimated  by  Rubner  after  the  above  fashion,  and  may  thus  be 
tabulated : 

CALORIFIC   VALUE   OF   PROTEIN   IN   NUTRITION 


Calories  Yielded 
by     Metabolism 
of  100  Grams  of 
Protein    in    the 
Body. 

Heat  Value  in 
Calories  of  Pro- 
tein Metabolism 
Yielding  i  Gm.  of 
N.  in  the  Ex- 
creta. 

After  protein  (washed  meat)  ingestion 

After  meat  ingestion 

442.4 

400.05 

384.2 

26.66 
25.98 

24.98 

If  we  know  the  amount  of  nitrogen  in  the  excreta  we  can 
calculate  from  these  standard  figures  of  Rubner  the  heat 
value  of  the  protein  metabolism  to  the  body.  Rubner  found 
that  the  heat  value  of  1  gram  of  pig's  fat  (lard)  was  9.423 
calories.  Since  fat  contains  76.5  per  cent,  of  carbon,  it  could 
be  calculated  that  for  every  gram  of  carbon  eliminated  in  the 
respiration,  which  was  the  result  of  fat  metabolism,  12.3 


INTRODUCTORY  4 1 

calories  must  have  been  liberated  in  the  body.  These  figures 
enabled  Rubner  to  calculate  the  amount  of  heat  liberated  by 
the  fasting  man  of  Pettenkofer  and  Voit,  whose  metabolism 
we  have  already  discussed.  The  N  excreted  was  multiplied 
by  24.98  and  the  fat  carbon  by  12.3  which  gave  the  total  heat 
value  of  the  period: 

Heat  from  protein  (11.33  Gm.  N  X  24.98) 283  Cal. 

Heat  from  fat  (169.95  C  X  12.3) 2091  Cal. 

Total  heat  value  of  the  metabolism  as  calculated.    2374  Cal. 

Rubner  applied  such  calculations  as  these  to  the  material 
at  hand  in  the  literature  of  the  time,  and  discovered  that  the 
heat  value  of  the  metabolism  of  the  resting  individual  is  propor- 
tional to  the  area  of  the  surface  of  his  body.  For  example,  a 
man  in  starvation,  or  on  a  medium  diet,  an  infant  at  the  breast, 
and  a  starving  dog  were  shown  to  give  off  similar  quantities 
of  heat  per  square  meter  of  surface.  To  these  Rubner 
subsequently  added  the  results  of  his  researches  upon  a 
dwarf.     The  following  tables  illustrate  this  point: 

Yield  of  Calories  per  Sq.  M. 
Surface  in  24  Hours. 

Adult  man  in  starvation 1134 

Dog  in  starvation 1112 

Adult  man  on  a  medium  mixed  diet 1189 

Breast-fed  infant 1221 

Dwarf  (weight  =  6.6  Kg.)  medium  mixed  diet 1231 

This  law,  that  an  animal  in  starvation  or  on  a  medium 
diet  and  at  an  environmental  temperature  of  i8°  gives  off 
the  same  quantity  of  heat  per  square  meter  of  surface,  can  be 
extended  so  that  it  applies  to  all  warm-blooded  animals. 
Thus  E.  Voit1  has  collected  data  for  the  following  table: 

Calories. 
Weight  in  Kg.  Per  Kilo.    Per  Sq.  M.  Surface. 

Pig 128.0  19. 1  1078 

Man 64.3  32.1  1042 

Dog 15.2  51.5  1039 

Goose 3.5  66.7  967 

Fowl 2.0  71.0  947 

Mouse 0.018  654.0  1188 

1  E.  Voit:   "Zeitschrift  fur  Biologie,"  1901,  xli,  120. 


42  SCIENCE    OF   NUTRITION 

Recent  work  has  confirmed  the  validity  of  this  "law  of 
surface  area,"  but  has  somewhat  modified  the  idea  of  the 
conditions  under  which  it  finds  expression  (see  Chapter  IV). 

Rubner  from  his  work  on  protein  considered  that  the 
heat  value  of  i  gram  in  an  average  mixed  diet  might  well  be 
placed  at  4.1  calories.  Of  course,  such  a  mixed  diet  would 
contain  casein  (4.4  cal.),  the  organic  substance  of  meat  (4.233 
cal.),  and  vegetable  proteins  (3.96  cal.).  The  daily  food 
allowance  for  animal  protein  was  put  at  60  per  cent.,  for 
vegetable  protein  at  40  per  cent.,  of  the  total  protein  in  the 
mixed  dietary.  For  the  value  of  neutral  fats  Stohmann's 
figures  for  olive  oil,  fat  of  animal  tissue,  and  butter  fat  were 
averaged  as  follows: 

Olive  oil 9-384  Calories  per  Sm. 

Animal  tissue  fat 9-372        "  " 

Butter  fat 9-179        "  " 

Average 9.3 12       " 

For  the  heat  value  of  i  gram  of  fat  in  a  mixed  diet  Rubner 
therefore  adopted  the  value  9.3. 

The  following  heat  values  have  been  found  for  carbohy- 
drates: 

Stohmann.  Rubner. 

Glucose 3.692  3.755 

Lactose 3-877 

Sucrose 3-959  4.001 

Starch 4. 116 

The  variations  in  heat  value  are  principally  due  to  variations 
in  the  water  content  of  the  different  molecules.  Considering 
the  predominating  importance  of  starch  in  the  average  diet, 
Rubner  gave  the  value  of  4.1  to  the  group  of  carbohydrates  in 
the  foods. 

Rubner's  "standard  values"  have  been  widely  used 
throughout  the  world  in  determining  the  average  fuel  value  of 
a  mixed  diet.     They  are: 

1  gram  of  protein 4.1  Calories. 

1  gram  of  fat 9.3        " 

1  gram  of  carbohydrate 4. 1        " 


INTRODUCTORY 


43 


Their  accuracy  has  been  verified  by  Rubner1  in  the  most 
careful  manner. 

Rubner,2  still  working  in  the  Munich  laboratory,  showed 
that  if  the  diet  were  increased  from  a  medium  to  an  abundant 
amount,  the  metabolism  as  indicated  by  the  heat  production 
rose.  This  dynamic  action  resulting  from  the  excessive 
ingestion  of  a  food-stuff  was  greatest  with  protein. 

Finally  Rubner,  in  his  own  laboratory  at  Marburg, 
evolved  an  animal  calorimeter  which  could  accurately  measure 
the  amount  of  heat  a  dog  produced  in  twenty-four  hours. 
The  dog  was  placed  within  the  chamber  of  the  calorimeter, 
and  this  chamber  was  attached  to  a  respiration  apparatus,  so 
that  the  metabolism  could  be  calculated  according  to  the 
method  of  Pettenkofer  and  Voit.  From  the  metabolism  the 
heat  production  could  be  estimated.  The  results  were  a 
triumphant  demonstration  of  the  truth  of  the  law  of  the 
conservation  of  energy.  The  amount  of  heat  calculated  by 
Rubner3  as  the  quantity  that  should  have  been  derived  from 
the  metabolism  of  the  dog  during  the  day  spent  in  the  calor- 
imeter was  the  amount  actually  given  off  by  the  dog  to  the 
calorimeter.  The  metabolism,  the  cause  of  the  motions  of 
life,  was  the  source  of  the  heat-loss  of  the  body.  The  results 
achieved  constitute  a  final  verification  of  the  methods  of  calcu- 
lating the  total  metabolism  originated  by  Pettenkofer  and  Voit. 

An  epitome  of  Rubner's  experiments  is  here  presented : 

COMPARISON  OF  ESTIMATED  HEAT  FROM  METABOLISM  WITH 
HEAT  ACTUALLY  PRODUCED 


Food. 

Number  of 
Days. 

Heat  Calcu- 
lated from 
Metabolism. 

Heat  Directly 
Determined. 

Difference 
in  Percent- 
age. 

Starvation 

Fat 

{      \ 

5 
\          8 

I           12 
\              6 

1296.3 
109 1.2 
1510.1 
2492.4 

3985-4 
2249.8 
4780.8 

I305-2     \ 
1056.6     / 
1498.3 
2488.0 

3958.4 
2276.9     \ 

4769-3     / 

-1.42 
—  0.97 

Meat  and  fat 

Meat 

—  0.42 
+043 

7 

1  Rubner:    "Zeitschrift  fur  Biologie,"  Festschrift  zu  Voit,  1901,  xlii,  261. 

2  Rubner:    "Sitzungsberichte  der  bayer.  Akademie,"  1885,  p.  454. 

3  Rubner:    "Zeitschrift  fur  Biologie,"  1894,  xxx,  73. 


44  SCIENCE    OF   NUTRITION 

Following  Rubner,  Atwater,  at  one  time  a  pupil  of  Voit, 
with  the  aid  of  Rosa,  the  physicist,  constructed  a  large 
calorimeter  capable  of  measuring  to  a  nicety  the  amount  of 
heat  given  off  by  a  man  living  in  it.  This  apparatus  confirmed 
Rubner's  experiments  and  has  shown  that  the  energy  expended 
by  a  man  in  doing  any  work,  such  as  bicycle-riding,  is  exactly 
equal  to  the  energy  set  free  by  metabolism  in  the  body. 
Ex  nihilo  nihil  fit. 

This  apparatus  was  the  product  of  many  years  of  labor 
and  its  cost  was  borne  by  the  United  States  Government. 
Armsby  has  completed  a  similar  one  for  use  with  cattle  for 
the  Agricultural  Station  of  the  State  of  Pennsylvania.  Benedict 
with  great  success  has  extended  Atwater's  work  in  the  notable 
Nutrition  Laboratory  of  the  Carnegie  Institution  in  Boston. 
This  is  housed  in  a  new  building  splendidly  equipped  with 
apparatus  for  the  simultaneous  determination  of  metabolism 
and  heat  production.  The  work  has  been  still  further  ex- 
tended by  the  construction  for  the  Physiological  Laboratory 
of  the  Cornell  University  Medical  College  in  New  York  City 
of  a  small  respiration  calorimeter1  suitable  for  use  with  babies, 
dwarfs,  and  dogs,  and  of  the  Sage  respiration  calorimeter2 
constructed  in  Bellevue  Hospital  by  the  Russell  Sage  Insti- 
tute of  Pathology  for  the  determination  of  metabolism  in 
diseased  conditions.  The  two  machines  have  been  under  the 
general  management  of  the  writer.  These  elaborate  and 
costly  devices  prove  and  confirm  the  general  laws  of  metab- 
olism in  the  body  enunciated  above,  through  a  knowledge 
of  which  alone  proper  systems  of  nutrition  for  people  under 
various  conditions  may  be  devised  (see  p.  56).  The  Amer- 
ican Indian  when  first  shown  a  watch  thought  it  was  alive. 
We,  on  the  other  hand,  have  come  to  look  upon  the  living 
organism  as  a  machine.  Like  the  moving  locomotive,  we 
burn  more  if  we  are   to   attain  a  faster  speed,  or  if  we  are 


1  Williams:    "Journal  of  Biological  Chemistry,"  1012,  xii,  317. 

2  Riche  and  Soderstrom:   "Archives  of  Internal  Medicine,"  1915,  xv,  805; 
Lusk,  same  "Archives,"  p.  793. 


INTRODUCTORY  45 

to  keep  all  parts  warm  in  the  winter's  cold.  In  both  cases 
the  motion  and  the  heat  are  derived  from  the  power  in 
the  fuel.  The  casual  observer  sees  the  moving  train,  but  the 
expert  engineer  alone  knows  how  and  why  the  wheels  go 
round.  The  physiologist  busies  himself  answering  the  similar 
how  and  why  regarding  the  mechanism  of  living  things. 

Before  taking  up  the  details  of  the  work  we  may  copy  the 
last  general  pronouncement  of  Voit1  upon  the  subject  of 
metabolism.     It  reads: 

"The  unknown  causes  of  metabolism  are  found  in  the  cells 
of  the  organism.  The  mass  of  these  cells  and  their  power  to 
decompose  materials  determine  the  metabolism.  It  is  abso- 
lutely proved  that  protein  fed  to  the  cells  is  the  easiest  of  all 
the  food-stuffs  to  be  destroyed,  next  carbohydrates,  and  lastly 
fat.  The  metabolism  continues  in  the  cells  until  their  power 
to  metabolize  is  exhausted.  All  kinds  of  influences  may  act 
upon  the  cells  to  modify  their  ability  to  metabolize,  some 
increasing  it  or  others  decreasing  it.  To  the  former  category 
belong  muscular  work,  cold  of  the  environment  (in  warm- 
blooded animals),  abundant  food,  and  warming  the  cells.  To 
the  latter,  cooling  the  cells,  certain  poisons,  etc. 

"In  speaking  of  the  power  of  the  cells  to  metabolize,  I  have 
not  meant  thereby,  as  may  be  seen  from  all  my  writings,  that 
the  cells  must  always  use  energy  in  order  to  metabolize,  but 
rather  I  have  understood  thereby  the  sum  of  the  unknown 
causes  of  the  metabolic  ability  of  the  cells — as  one  speaks  of 
the  fermentative  'power'  of  yeast  cells. 

"The  metabolism  of  the  different  food-stuffs  varies  with  the 
quality  and  quantity  of  the  food.  Protein  alone  may  burn,  or 
little  protein  and  much  carbohydrate  and  fat.  I  have  deter- 
mined the  amount  of  the  metabolism  of  the  various  food-stuffs 
under  the  most  varied  conditions.  All  the  phases  of  metab- 
olism originate  from  processes  in  the  cells.  In  a  given  con- 
dition of  the  cells  available  protein  may  be  used  exclusively 
if  enough  be  furnished  them.     If  the  power  of  the  cells  to 

1  Voit:    "Munchener  medizinische  Wochenschrift,"  1902,  xlLx,  233. 


46  SCIENCE    OF   NUTRITION 

metabolize  is  not  exhausted  by  the  protein  furnished,  then 
carbohydrates  and  fats  are  destroyed  up  to  the  limit  of  the 
ability  of  the  cells  to  do  so. 

"From  this  use  of  materials  arise  physical  results,  such  as 
work,  heat,  and  electricity,  which  we  can  express  in  heat 
units.     This  is  the  power  derived  from  metabolism. 

"It  is  possible  to  approach  the  subject  in  the  reverse  order, 
that  is,  to  study  the  energy  production  (Kraftwechsel)  and  to 
draw  conclusions  regarding  the  metabolism  (Stoffwechsel).  It 
is  perfectly  possible  to  say  that  the  requirement  of  energy  in 
the  body  or  the  production  of  the  heat  necessary  to  cover  heat 
loss,  or  for  energy  to  do  work,  are  controlling  factors  of  the 
metabolism;  since  on  cooling  the  body  or  on  working  cor- 
respondingly more  matter  is  destroyed.  But  one  must  not 
conclude  that  the  loss  of  body  heat  and  muscular  work  are  the 
immediate  causes  of  this  increased  metabolism.  The  causes 
lie  in  the  peculiar  conditions  of  the  organism,  and  muscle 
work  and  loss  of  heat  are  merely  factors  acting  favorably  upon 
those  causes,  raising  the  power  of  the  cells  to  metabolize.  In 
virtue  of  this  more  is  destroyed,  and  secondarily  the  power  to 
work  and  increased  heat  production  are  determined. 

"The  requirement  for  energy  cannot  possibly  be  the  cause 
of  metabolism,  any  more  than  the  requirement  for  gold  will 
put  it  into  one's  pocket.  Hence  the  production  of  energy  has 
a  very  definite  upper  limit,  which  is  afforded  by  the  ability 
of  the  cells  to  metabolize.  If  the  cells  will  metabolize  no  more, 
then  further  increase  of  work  ceases  even  in  the  presence  of 
direst  necessity;  and  this  is  also  the  case  with  the  heat  produc- 
tion, even  though  it  were  very  necessary,  and  we  were  likely 
to  freeze. 

"I  therefore  maintain  my  'older'  point  of  view,  that  of  pure 
metabolism,  in  order  to  explain  the  phenomena  of  nutrition.  I 
am  convinced  that  it  is  the  right  way,  and  that  the  clearest 
and  most  unifying  development  will  be  possible  as  one  inves- 
tigates what  substances  are  destroyed  under  different  circum- 
stances, such  as  the  performance  of  work,  and  loss  of  heat, 


INTRODUCTORY  47 

and  how  much  of  the  different  materials  must  be  fed  to  main- 
tain the  body  in  condition." 

ADDENDUM  CONCERNING  THE  NATURE  OF  THE  FECES 

In  the  historic  introduction  just  given  it  has  been  shown 
that  the  nitrogen  of  the  urine  and  feces  can  be  made  a  measure 
for  the.  determination  of  protein  metabolism.  It  is  easy  to 
comprehend  that  urinary  constituents,  such  as  urea,  uric  acid, 
the  purin  bases,  creatinin,  etc.,-  are  derived  from  the  metab- 
olism of  flesh  in  the  body,  whether  the  flesh  be  the  body's  own 
or  that  of  an  animal  fed  to  it.  But  the  intestinal  canal  where 
the  feces  are  formed  is  a  long  tube  open  at  both  ends,  through 
which  may  pass  the  nitrogen  gas  of  the  air  swallowed  and 
indigestible  substances  such  as  hair,  tacks,  etc.  In  diarrhea 
the  curds  of  milk,  pieces  of  undigested  meat  or  bread,  and 
large  quantities  of  fat  are  in  evidence.  These  common 
observations  would  seem  to  justify  the  popular  supposition 
that  normal  feces  are  made  up  of  the  undigested  residues  of 
the  food-stuffs.  In  truth,  however,  this  is  very  far  from  the 
fact.  The  feces  are  chiefly  the  unabsorbed  residues  of  in- 
testinal excretions. 

The  collection  of  the  feces  for  a  given  period  of  nutrition  is 
more  difficult  than  the  collection  of  the  urine.  The  urine  may 
be  collected  every  two  hours  and  may  fairly  represent  the 
protein  metabolism  of  the  time,  but  the  feces  are  normally 
passed  but  once  a  day  by  a  man  on  a  mixed  diet,  and  only 
once  in  five  days  by  a  dog  fed  with  meat.  Furthermore, 
particles  fed  to  a  man  are  not  usually  passed  in  his  feces  for 
two  or  three  days.  The  feces  formed  during  a  certain  digestive 
period  might  therefore  leave  the  body  two  or  three  days  after 
the  urine  was  drawn  from  the  bladder.  To  obtain  clear 
results  Voit  fed  a  dog  with  60  grams  of  bones  in  a  preliminary 
diet  eighteen  hours  before  the  regular  feeding  began.  These 
bones  yielded  a  whitish  mark  in  the  fecal  excretion.  All  feces 
subsequent  to  the  mark  were  attributed  to  the  diet  used  in  the 
experiment.     At  the  conclusion  of  the  experiment  a  second 


48  SCIENCE    OF   NUTRITION 

diet  containing  bones  was  given.  The  whitish  excrement 
formed  from  this  indicated  the  end  of  the  feces  of  the  period. 
For  the  same  purpose  Rubner1  gave  milk  (2  liters)  to  a  man, 
the  last  portion  of  the  milk  being  taken  eighteen  hours  before 
the  commencement  of  a  period  of  feeding.  The  milk  feces 
give  a  distinct  whitish  dividing  line.  A  teaspoonful  of  lamp- 
black may  also  be  readily  made  use  of  in  man  and  in  animals. 
Cremer2  uses  freshly  precipitated  silicic  acid  (10  to  25  grams 
mixed  with  40  to  100  grams  fat)  instead  of  bones.  This  gives 
excellent  results,  as  it  avoids  the  albuminoid  nitrogen  in  the 
bones,  and  is  of  great  advantage  if  the  calcium  or  other  ash 
constituents  of  the  feces  are  to  be  determined. 

In  the  fundamental  experiments  Voit  found  that  a  fasting 
dog  weighing  30  kilograms  excreted  1.88  grams  of  dry  fecal 
matter  per  day,  containing  0.15  gram  of  nitrogen.  Evidently 
these  starvation  feces  are  not  derived  from  the  food,  but  must 
be  derived  from  the  matter  passed  from  the  body  into  the 
intestinal  canal.  An  analogous  condition  is  found  in  the 
intestinal  tract  of  the  newborn  infant.  The  meconium  con- 
sists principally  of  the  unabsorbed  residues  of  the  bile,  of 
glycocholic,  taurocholic,  and  fellic  acids,  of  cholesterin  and 
lecithin,  colored  by  bilirubin  or  biliverdin.  The  absence  both 
of  putrefaction  and  the  acid  of  the  gastric  juice  prevents  the 
breaking  up  and  reabsorption  of  many  of  these  substances, 
processes  which  occur  soon  after  birth.  The  fasting  dog  of  30 
kilograms,  mentioned  above,  excreted  1.88  grams  of  dry 
feces,  but  a  fasting  dog  of  20.3  kilograms  may  yield  4.3  grams 
of  dry  bile  solids  in  twenty-four  hours.3  The  ordinary  starva- 
tion feces  therefore  cannot  consist  of  the  total  of  the  excretions 
from  the  body  into  the  digestive  tract,  but  are  rather  their 
unabsorbed  remainder. 

When  meat  was  given,  Bischoff  and  Voit4  found  that  the 
production  of  feces  was  not  proportional  to  the  amount  of 

1  Rubner:    "Zeitschrift  fur  Biologie,"  1879,  xv,  119. 

2  Cremer:   Ibid.,  1897,  xxxv,  391. 

3  Voit:   Ibid.,  1894,  xxx,  548. 

4  Bischoff  and  Voit:   "Die  Ernahrung  des  Fleischfressers,"  i860,  p.  291. 


INTRODUCTORY  49 

meat.  A  compilation  of  the  data  given  by  Friedrich  Miiller1 
illustrates  the  average  amount  of  dry  feces  produced  by  a 
dog  weighing  35  kilograms  after  feeding  different  quantities 
of  meat: 


:  in  Grams. 

Fecal  Solids. 

Fecal  N 

0 

2.0 

O.15 

500 

5-i 

o-33 

1000 

9.2 

0.60 

1500 

10.2 

0.66 

2000 

11. 1 

0.72 

2500 

15-4 

1. 00 

The  feces  had  the  same  pitch-black  color  as  starvation  feces 
and  were  similar  to  the  2  grams  of  feces  which  would  have 
been  produced  by  the  same  dog  had  be  been  starving.  No 
muscle-fibers  and  no  protein  could  be  detected.  It  seemed 
clear  that  the  meat  feces  differed  from  the  starvation  feces 
mainly  in  quantity,  and  that  this  quantity  was  larger  because 
the  secretions  into  the  intestines  had  been  stimulated  by  the 
passing  food. 

Fat  ingested  with  the  meat  in  moderate  quantities  had  no 
influence  on  the  feces.  Nor  had  sugar,  unless  its  fermentation 
produced  diarrhea.  Bread  somewhat  increased  the  volume 
of  the  feces,  which  contained  some  undigested  starch.  Here 
an  irritation  of  the  intestinal  canal  by  the  bread  produced  a 
larger  excretion  into  the  intestines. 

The  source  of  the  feces  was  further  investigated  by  Her- 
mann,2 whose  work  was  later  elaborated  by  Fritz  Voit.3  The 
latter  separated  a  loop  of  the  intestine  about  a  third  of  a 
meter  long  from  the  rest  of  the  intestine  of  a  starving  dog. 
Both  ends  of  the  loop  were  tied  and  the  loop  remained  in  the 
abdomen  in  connection  with  its  normal  nerve  and  blood  supply. 
The  two  ends  of  the  remaining  portion  were  reunited.  After 
a  few  days  food  could  be  given  and  the  normal  excretion  of 
feces  took  place.  After  three  weeks  the  animal  was  killed. 
It  was  found  that  the  isolated  loop  contained  a  thick,  fecal- 

1  von  Miiller:  "Zeitschrift  fur  Biologie,"  1884,  xx,  340. 

2  Hermann:   "Pfliiger's  Archiv,"  1890,  xlvi,  93. 

3  F.  Voit:   "Zeitschrift  fur  Biologie,"  1892,  xxix,  325. 


5° 


SCIENCE    OF   NUTRITION 


like  mass.  It  was  found  that  the  dry  solids  of  this  mass 
contained  the  same  percentage  of  nitrogen  as  did  the  feces 
passed  by  the  dog  during  the  three  weeks  of  the  experiment. 
It  was  also  calculated  that  the  amount  of  nitrogen  excreted 
through  the  wall  of  the  intestinal  loop  was  nearly  the  same 
per  unit  of  area  as  the  amount  of  nitrogen  in  the  feces  when 
spread  over  the  surface  of  the  whole  of  the  rest  of  the  intes- 
tine.    The  following  table  shows  this: 


Percentage  of  N 
in  the  Dry 
Substance. 

Grams  N  from  i  Sq. 
M.  in  24  Hours. 

Feces. 

Content 
of  Loop. 

Feces. 

Content, 
of  Loop. 

Dog  I 

5.62 
5-27 

5-32 
0.88 

0.28 
0.25 

O.22 

Dog  III 

0.32 

The  loop  contained  fat  and  fatty  acids  in  greater  quantity 
than  is  normally  found  in  feces,  which  may  indicate  a  usual 
reabsorption  of  these  substances. 

Fritz  Voit  has  therefore  shown  that  the  excretion  of  sub- 
stances from  an  isolated  loop  of  the  intestine  produces  a  mass 
of  a  similar  constitution  and  of  nitrogen  output  equal  to  that 
in  the  normal  intestine  of  the  same  animal  through  which 
meat  and  fat  were  passing.  He  therefore  concludes  that  the 
feces  are  derived  principally  from  the  substances  excreted 
through  the  wall  of  the  intestine.  The  nitrogen  so  excreted 
is  as  much  to  be  considered  a  product  of  protein  metabolism 
as  is  the  nitrogen  of  urea.  It  is  regretable  that  very  little 
is  known  regarding  the  chemistry  of  these  nitrogenous  com- 
pounds excreted  into  the  intestine. 

It  has  been  seen  that  the  feeding  of  simple  food-stuffs,  such 
as  meat,  fat,  and  sugar,  scarcely  influenced  the  composition  of 
the  feces  in  the  dog.  In  herbivora  we  pass  to  another  extreme. 
Here  vast  amounts  of  cellulose  are  eaten,  a  great  part  of  which 
is  never  disintegrated,  but  even  after  long  retention  in  the 


INTRODUCTORY  5 1 

capacious  intestinal  tract  is  passed  in  the  feces.  After  giving 
an  ordinary  feed  to  a  cow  one  may  find  as  much  nitrogen 
in  the  feces  as  in  the  urine.  Under  such  conditions  as  these 
the  very  voluminous  feces  evidently  do  consist  largely  of  the 
undigested  residues  of  the  fodder.  Armsby  and  Fries1  have 
shown  that  only  45  per  cent,  of  the  energy  contained  in  hay  is 
of  actual  use  in  cattle  feeding.  The  waste  in  the  feces  reaches 
41  per  cent.,  in  the  urine  7.25,  and  in  methane  gas  6.75  per 
cent,  of  the  total  energy  content. 

Concerning  the  fecal  production  in  man,  it  has  been  found 
that  Cetti2  excreted  3.8  grams  of  dry  fecal  solids  per  day  during 
a  fast  of  ten  days,  Breithaupt  2  grams,  and  a  medical  student3 
2.2  grams,  less  in  reality  than  would  a  dog  of  similar  size. 
Benedict4  states  that  he  was  unable  to  find  any  evidence  of  the 
formation  of  feces  during  a  seven-day  fast  in  man. 

Rieder5  gave  a  man  a  diet  containing  starch,  sugar,  and 
lard  from  which  a  cake  was  baked.  The  food  contained  no 
nitrogen,  but  the  fecal  excretion  was  0.54,  0.87,  and  0.78  gram 
of  nitrogen  per  day,  contrasting  with  0.316  gram  from  Cetti, 
0.1 13  from  Breithaupt,  and  0.13  from  a  medical  student  during 
fasting.  The  food,  even  though  it  contains  no  protein, 
stimulates  the  fecal  production. 

Wallace  and  Salomon6  have  administered  250  grams  of 
cane-sugar  daily  to  normal  persons  and  to  patients  suffering 
from  intestinal  diarrhea,  and  have  determined  the  amount  of 
fecal  nitrogen  during  periods  of  two  or  three  days.  The 
sugar  was  given  in  doses  of  50  grams  dissolved  in  300  c.c.  of 
water  and  flavored  with  fruits,  such  as  apple  and  lemon,  or 
with  wine.     Their  results  with  this  diet  were  as  follows: 

1  Armsby  and  Fries:  Bulletin  101,  1908,  Bureau  of  Animal  Industry,  U.  S. 
Dept.  of  Agriculture. 

2Lehmann,  Muller,  I.  Munk,  Senator,  Zuntz:  "Virchow's  Archiv,"  1893, 
Bd.  cxxxi,  Suppl.  Heft. 

3  Johansson,  Landergren,  Sonden,  Tigerstedt:  "Skandin.  Archiv  fur 
Physiologic,"  1897,  vii,  29. 

4  Benedict:   "Influence  of  Inanition  on  Metabolism,"  Carnegie  Institution, 

1907,  P-  345- 

5  Rieder:    "Zeitschrift  fur  Biologie,"  1884,  xx,  378. 

6  Wallace  and  Salomon:   "Medizinische  Klinik,"  1909,  v,  579. 


52  SCIENCE    OF   NUTRITION 

N  in  Feces  per  Day. 
Grams. 

Normal  man 0.539 

"    0.380 

Tuberculous  ulceration  of  intestine 3-Q75 

4.186 

Cancer  of  intestine 1.74 

"        1-974 

Catarrh  of  intestine  (severe) 1.464 

"      1.087 

It  is  evident  that  the  quantity  of  fecal  nitrogen  eliminated 
in  intestinal  diseases  is  largely  increased. 

It  has  been  stated  that  Voit  early  noticed  the  occurrence  of 
starch  particles  in  the  feces.  A  large  number  of  experiments 
have  been  made  to  test  the  digestibility  of  the  various  vege- 
tables and  cereals.  Rubner1  fed  an  able-bodied  soldier  on 
3078  grams  of  variously  cooked  potatoes  daily  and  found 
pieces  of  potatoes  in  the  feces.  He  notes  that  an  inhabitant 
of  Ireland  will  eat  4500  grams  of  potatoes  a  day.  Friedrich 
Muller2  writes  that  after  the  ingestion  of  a  large  quantity  of 
bread  the  feces  may  have  practically  the  same  composition 
as  bread. 

The  better  understanding  of  this  question  of  the  digesti- 
bility of  the  carbohydrates  has  come  through  the  work  of 
Prausnitz3  and  his  associates,  Moeller  and  Kermauner. 
Moeller  found  that  no  starch  appeared  in  the  feces  after  feed- 
ing well-cooked  white,  rye,  and  graham  bread,  rice  or  potatoes 
(even  when  fed  in  pieces) ,  or  legumes  when  they  were  prepared 
in  the  form  of  puree.  Legumes  not  in  the  form  of  puree,  such 
as  string  beans  eaten  as  salad,  may  resist  the  action  of  the 
digestive  juices  so  that  the  starch  contents  of  the  cell  are 
untouched,  and  the  vegetable  cells  appear  in  the  feces.  These 
facts  explain  the  appearance  of  bread  in  the  feces  if  the  bread 
be  badly  cooked,  or  if  such  a  "heavy"  bread  as  pumpernickel 
be  eaten.  The  imperfectly  cooked  bread  contains  starch 
granules  whose  coverings  are  impermeable  to  the  digestive 
juices,  as  are  also  many  of  those  in  the  unbolted  rye  of  pum- 
pernickel. 

1  Rubner:   "Zeitschrift  fur  Biologie,"  1879,  xv,  146. 

2Fr.  Muller:   Ibid.,  1884,  xx,  375.        3  Prausnitz:   Ibid.,  1897,  xxxv,  335. 


INTRODUCTORY 


53 


Prausnitz  finds  that  if  a  man  be  put  on  a  rice  diet  and  then 
meat  be  substituted  for  most  of  the  rice,  the  composition  of  the 
feces  does  not  vary  with  the  diet.  Such  feces  he  calls  normal 
feces.  They  may  contain  a  negligible  quantity  of  fibers  of 
meat  (Kermauner)  or  of  cellulose  from  the  rice. 

The  feces  of  6  persons  placed  alternately  on  meat  and  rice 
diets  yielded  normal  feces,  the  percentage  composition  of  the 
dry  solids  of  which  was  as  follows : 

COMPOSITION  OF  FECES  ON  DIFFERENT  DIETS 


No. 

Person. 

Principal  Food. 

N%. 

Ether  Extract 
%. 

Ash  %. 

I 

H. 

Rice 

8.83 

12.43 

15-37 

2 

H. 

Meat 

8-75 

15.96 

14.74 

3 

M. 

Rice 

8-37 

18.23 

11.05 

4 

M. 

Meat 

9.16 

16.04 

12.22 

5 

W.  P. 

Rice 

8-59 

15.89 

12.58 

6 

W.  P. 

Meat 

8.48 

17-52 

13-13 

7 

J.  Pa. 

Rice 

8.25 

14-47 

8 

J.  Pa. 

Meat 

8.16 

15.20 

9 

F.  Pi. 

Rice 

S.70 

16.09 

xo 

F.  Pi. 

Meat 

9-°5 

15-14 

ii 

Vegetarian. 

Rice 

.    8.78 

18.64 

12.01 

Average, 

8.65 

16.39 

13.82 

It  is  seen  from  this  that  whether  the  food  solids  contain  1.5 
per  cent.  N,  as  in  rice,  or  ten  times  that,  as  in  meat,  the  com- 
position of  the  feces  remains  uninfluenced.  Normal  feces 
result  from  the  eating  of  any  food  which  is  completely  digested 
and  absorbed.  In  all  such  cases  these  feces  have  the  same 
composition  and  are  derived  from  the  intestinal  wall.  It  is 
therefore  not  astonishing  that  a  vegetarian  of  many  years' 
standing  produced  the  same  kind  of  feces  when  fed  on  rice  as 
did  the  other  men.  The  same  quality  of  feces  has  been  ob- 
tained after  giving  good  bread. 

In  this  connection  it  is  interesting  to  note  that  the  heat 
value  of  1  gram  of  human  feces  is  very  constant  whether  the 
person  is  on  a  meat  diet  or  a  medium  mixed  diet.  Rubner1 
gives  the  heat  value  of  1  gram  of  organic  matter  in  the  feces 

1  Rubner:   "Die  Gesetze  des  Energieverbrauchs,"  1902,  p.  35. 


54  SCIENCE    OF   NUTRITION 

of  a  man  on  a  meat  diet  at  6.403  cal.,  while  on  a  mixed  diet 
1  gram  varies  between  6.061  and  6.357  cal.  The  average 
fuel  value  of  feces  is  therefore  6.2  calories  per  gram  of  dry- 
organic  substance,  and  this  changes  only  when  there  is  a  poor 
utilization  of  the  food.1  According  to  Lorisch,2  one  may 
calculate  the  approximate  heat  value  of  feces  by  reckoning 
the  nitrogen  therein  as  protein  nitrogen  and  multiplying  the 
amounts  of  "protein,"  "fat,"  and  carbohydrate  present  by 
their  usual  heat  value.  The  sum  of  these  is  said  to  give  a 
rough  estimate  of  the  calorific  loss  through  the  feces. 

After  eating  pumpernickel,  bad  bread,  or  string  beans  the 
waste  of  undigested  residues  of  these  substances  may  appear 
in  the  feces,  changing  its  composition  and  lowering  its  per- 
centage of  nitrogen  content. 

In  general,  Prausnitz  finds  no  difference  between  the 
digestibility  and  absorbability  of  animal  and  vegetable  foods. 
Meat,  rice,  and  bread  from  flour  are  all  digested  and  absorbed. 
The  ordinary  feces  indicate  whether  a  given  food  is  a  small  or  a 
great  feces  builder,  not  how  much  or  how  little  food  has  been 
used  for  the  organism. 

The  value  in  such  foods  as  cabbage,  string  beans,  cauli- 
flower, and  the  like  lies,  aside  from  their  flavor,  in  the  fact  that 
their  indigestible  waste  may  enhance  peristalsis  in  the  intestine. 
Their  food  value  is  small,  and  if  given  to  those  with  weak 
digestions,  is  dubious.  Mendel3  points  out  that  edible  car- 
bohydrate substances,  like  Iceland  moss,  agar-agar,  Jerusalem 
artichokes,  and  inulin,  are  scarcely  attacked  by  the  digestive 
juices  and  therefore  have  little  or  no  direct  nutritive  function. 
He4  also  finds  that  the  proteins  of  mushrooms  are  not  digested 
in  the  organism. 

The  part  played  by  bacteria  in  the  composition  of  the 
feces  has  been  variously  estimated.     Lissauer,5  working  in 

1  Rubner:   v.  Leyden's  "Handbuch  der  Ernahrungstherapie,"  IQ03,  p.  32. 

2  Lorisch:   "Zeitschrift  fiir  physiologische  Chemie,"  1904,  xli,  308. 

3  Mendel:   "Zentralblatt  fiir  Stoffwechsel,"  1008,  iii,  641. 

4  Mendel:   "American  Journal  of  Physiology,"  1898,  i,  225. 
6  Lissauer:   "Archiv  fiir  Hygiene,"  1906,  lviii,  145. 


INTRODUCTORY  55 

Rubner's  laboratory,  showed  that  two-thirds  of  the  fecal 
solids  were  soluble  in  alcohol.  In  the  insoluble  portion  mucin, 
food  protein,  and  the  remnants  of  cast-off  epithelial  cells, 
as  well  as  bacteria  were  found.  When  a  diet  of  meat  was 
given  to  a  man  food  residues  were  almost  entirely  wanting  in 
the  feces.  Though  the  quantity  of  bacteria  may  be  of  im- 
portance in  the  stools,  it  is  an  insignificant  factor  when  com- 
pared with  the  total  quantity  of  food  ordinarily  ingested. 
Lissauer  finds  the  following  percentages  of  bacteria  in  stools 
of  the  character  noted  below: 

Percentage  of  Dry  Bacterial 
Food.  Substances    in    Dry    Fecal 

Material. 

(Meat 4.3 

In  Man <  Mixed 8.7 

(.  Vegetable 10.5 

In  Does  I  Meat 54 

' '  \  Potatoes  and  bread 7.6 

In  Rabbits 1 .0 

In  Cows 16.7 

In  man  the  minimal  quantity  of  bacteria  composing  the 
stools  was  2.53  per  cent.,  the  maximum  13.54  per  cent.,  and 
the  average  was  8.7  per  cent,  of  the  total  solids.  Rubner  has 
calculated  that  1  gram  of  dry  bacterial  substance  contains 
0.1 14  gram  nitrogen.  Making  use  of  these  data,  Lissauer  has 
prepared  the  following  table  to  illustrate  the  part  which 
bacteria  may  play  in  the  fecal  nitrogen  elimination  of  man: 


Diet. 


Dry  Feces  N  Bacteria         Bacterial  N 

Gram.  Gram.  Gram.  Gram. 


Meat 17. 1  1. 12  0.73  0.08 

Mixed 30.0  2.9  2.86  0.33 

It  is  evident  that  the  quantity  of  bacterial  nitrogen  in  the 
feces  is  small  in  comparison  with  the  ordinary  intake  of  nitro- 
gen in  the  food.  Though  the  feces  apparently  swarm  with 
bacteria,  it  should  be  recalled  that  4,000,000,000  weigh  only  1 
milligram. 

It  may  be  added  that  Osborne  and  Mendel1  report  that 
70  per  cent,  of  the  nitrogen  of  the  rat's  feces  is  due  to  bacteria. 

1  Osborne  and  Mendel:  "Journal  of  Biological  Chemistry,"  1014,  xviii,  177. 


CHAPTER  II 

THE  ATWATER-ROSA  RESPIRATION  CALORIMETER 

A  respiration  calorimeter  is  an  apparatus  designed  for 
the  measurement  of  the  gaseous  exchange  between  a  living 
organism  and  the  atmosphere  which  surrounds  it,  and  the 
simultaneous  measurement  of  the  quantity  of  heat  produced 
by  that  organism. 

In  1892  Atwater  began  work  upon  a  calorimeter  which 
could  measure  the  heat  production  in  man,  the  first  description 
of  which  appeared  in  1897. x  The  initiative  in  the  undertaking 
rested  with  Atwater,  whereas  the  successful  completion  of  the 
apparatus  was  largely  due  to  the  physicist  Rosa.  The 
original  Atwater-Rosa  calorimeter  was  combined  with  a 
respiration  apparatus  of  the  type  designed  by  Pettenkofer, 
which  measured  only  the  carbon  dioxid  excretion  without 
determining  the  oxygen  intake. 

The  apparatus  represented  technical  perfection,2  as  was 
evidenced  by  the  fact  that  when  a  measured  amount  of  heat 
was  generated  by  an  electric  current  within  the  box  it  was 
determined  as  100.01  per  cent,  of  the  actual  value.  This  test 
of  accuracy  is  called  an  electric  check.  Also,  when  a  known 
quantity  of  alcohol  was  oxidized,  the  carbon  dioxid  recovered 
amounted  to  99.8  per  cent,  and  the  heat  to  99.9  per  cent,  of  the 
theoretic  value.  This  is  an  alcohol  check.  In  experiments 
with  men  the  work  frequently  lasted  during  a  period  of  several 
days.  The  method  of  computation  was  based  on  that  of 
Voit  and  Rubner,  i.  e.,  the  amount  of  protein  carbon  excreted 
was  calculated  from  the  nitrogen  excreted  in  the  urine  and 

1  Atwater  and  Rosa:  "Report  of  the  Storrs  Agricultural  Experiment  Sta- 
tion," 1897,  p.  212. 

2  Atwater  and  Benedict:  "Memoirs  of  the  National  Academy  of  Sciences," 
1002,  viii,  231. 

56 


THE   ATWATER-ROSA   RESPIRATION   CALORIMETER  57 

feces,  this  subtracted  from  the  total  carbon  excreted  in  the 
respiration,  urine,  and  feces  gave  the  total  non- protein  carbon  or 
that  attributable  to  carbohydrate  and  fat.  It  was  assumed 
that  all  the  carbohydrate  ingested  was  oxidized  and  that  after 
deducting  this  amount  the  excess  of  non-protein  carbon  was  de- 
rived from  the  metabolism  of  fat.  In  this  way  the  calories  from 
protein,  carbohydrate,  and  fat  were  computed.  The  validity 
of  this  method  is  shown  in  the  work  of  Atwater  and  Benedict 
by  the  average  results  per  day  of  forty  days  of  experimentation 
with  three  different  individuals  who  took  an  ordinary  mixed 
diet: 

Calories. 

Indirect  calorimetry 2717 

Direct  calorimetry 2723 

Difference 0.2  per  cent. 

Atwater  was  not  content  to  omit  the  determination  of 
oxygen,  and  turned  his  attention  to  this  important  problem. 
As  already  explained  (p.  29),  the  quantity  of  oxygen  required 
in  metabolism  depends  on  the  kind  of  material  oxidized  in  the 
organism,  and  the  relation  between  the  amount  of  oxygen 
absorbed  and  carbon  dioxid  eliminated  depends  on  the  same 
factor.  The  ratio  of  the  volume  of  carbon  dioxid  expired  to 
the  volume  of  oxygen  inspired  during  the  same  interval  of 
time  was  called  by  PfTiiger  the  respiratory  quotient. 

It  was  known  to  Lavoisier  that  any  volume  of  oxygen 
uniting  with  carbon  produced  the  same  volume  of  carbon 
dioxid.  Since  the  volume  of  oxygen  inspired  was  found  in 
his  experiments  to  be  larger  than  that  of  the  expired  carbon 
dioxid,  Lavoisier  concluded  that  a  portion  of  the  inspired 
oxygen  must  have  been  used  to  oxidize  hydrogen  in  the 
production  of  water.  Under  these  circumstances  the 
Volume  of2  would  be  less  than  unity.  The  carefully  executed 
experiments  of  Regnault  and  Reiset,  published  in  1849, 
showed  that  the  value  of  the  respiratory  quotient  depended 
on  the  nature  of  the  food  given  and  not  on  the  species  of 
animal.    They  found  that  the  respiratory  quotient  might  vary 


58  SCIENCE    OF   NUTRITION 

in  the  same  animal  from  1.02  to  0.64,  and  that  it  varied  with 
the  kind  of  food  taken,  but  was  constant  with  the  same  food. 
When  fowls  were  fed  with  corn  or  dogs  with  bread,  respiratory 
quotients  of  1.02  and  0.93,  respectively,  were  obtained.  The 
quotients  were  lower  when  a  meat  diet  was  given  and  still 
lower  than  this  when  the  animal  fasted.  The  low  quotients 
during  inanition  were  obtained  alike  with  herbivorous  and 
carnivorous  animals,  which  indicated  to  Regnault  and  Reiset 
that  these  animals  lived  upon  their  own  flesh  under  con- 
ditions not  unlike  those  existing  when  a  meat  diet  was 
taken. 

Turning  now  to  modern  analysis,  it  is  evident  that  when 
carbohydrate,  in  which  hydrogen  and  oxygen  are  always  present 
in  the  proportion  to  form  water,  is  oxidized,  the  respiratory 
quotient  will  be  unity.     One  may  express  the  process  thus: 

C6H1206  +  6O2  =  6CO2  +  6H20 

Since  equal  volumes  of  gases  at  the  same  temperature  and 
pressure  contain  equal  numbers  of  molecules  (Law  of  Avagadro, 
181 1)  it  is  evident  from  the  above  formula  that  one  volume 
of  oxygen  absorbed  produces  one  volume  of  carbon  dioxid 
during  carbohydrate  combustion.  Hence,  for  carbohydrate 
the  R.  Q.  =  1.00. 

When  fat  is  oxidized  oxygen  is  utilized  not  only  for  the 
production  of  carbon  dioxid,  but  also  for  the  oxidation  of 
hydrogen,  forming  water. 

This  is  evident  from  the  following  formula: 

C3H5(02C.CH2.CH.2.CH,.CHo.CH2.CH2.CH2.- 

CH,.CH2.CH2.CH2.CH2.CH2.CH2.CH3)3 

Tripalmitin. 

If  one  deducts  the  intramolecular  water  from  tripalmitin 
one  obtains  the  following: 

Tripalmitin CsiHgsOe 

Deduct  intramolecular  H20 H12O6 

Leaving  for  oxidation C51H86 


THE    ATWATER-ROSA    RESPIRATION    CALORIMETER  59 

This  on  oxidation  yields: 

2(C5iHsr,)  +  145O2  =  102CO2  +  86H2O 

102  volumes  CO2 

R.  Q.  =  ■  =  0.703 

145  volumes  O2 

Edible  fats  are  usually  mixtures  of  various  simple  fats, 
consisting  for  the  most  part  of  tripalmitin,  tristearin,  and 
triolein,  all  of  which  require  nearly  the  same  quantity  of 
oxygen  for  oxidation.  Lehmann,  Miiller,  Munk,  Senator,  and 
Zuntz1  analyzed  the  respiratory  quotient  which  should  be 
obtained  from  lard  as  follows: 

1  gram  lard  =  0.765  g.     C   +  0.119    g.  H  +  0.116  g.  O 

Deduct  intramolecular  water  0.0145  g-  H  -j-  0.116  g.  O 

0.765  g.     C  +  0.1045  g-  H 
Required  for  oxidation  2.040  g.     O   +  0.836    g.  O 


2.805  g-  C02  +  0.9405  g.  H20 


As  the  weight  of  the  oxygen  molecule  is  to  that  of  carbon 
dioxid  as  8  is  to  11,  the  respiratory  quotient  is  deduced, from 
the  relative  weights  as  follows: 

2.805  g-  C02       8 
R.  Q.  = X  -^  =  0.710 

2.876  g.    O2      11 

Zuntz2  later  slightly  changed  the  oxygen  value  so  that  the 
calculated  quotient  was  0.707.  A  still  more  recent  computa- 
tion by  Zuntz3  for  human  fat  shows  a  respiratory  quotient  of 
0.713.  The  respiratory  quotient  of  fat  is,  therefore,  very 
constant. 

The  respiratory  quotient  for  protein  is,  for  the  most  part, 
the  resultant  of  the  oxidation  of  the  various  amino-acids  of 
which  protein  is  composed  (see  p.  77).  This  quotient,  as 
calculated  by  Zuntz,  is  based  upon  the  careful  analytic  data 

^Lehmann,  Miiller,  Munk,  Senator,  and  Zuntz:  "Virchow's  Archiv,"  1893, 
cxxxi,  Suppl.  Bd.,  p.  131. 

2  Zuntz:   "Pfliiger's  Archiv,"  1807,  lxviii,  201. 

3  Zuntz:  "Zuntz  und  Loewy's  Lehrbuch  der  Physiologie  des  Menschen," 
2d  edition,  Leipzig,  1913,  p.  644. 


60  SCIENCE   OF   NUTRITION 

prepared  by  Rubner,  already  described.  Zuntz,  however, 
substracted  the  fat  in  the  feces  from  the  material  attributable 
to  protein  metabolism.  A  recent  computation  by  Loewy1 
is  as  follows: 

ioo  grams  meat  protein  contain: 

52.38    g.  C     7.27    g.  H  22.68    g.  O     16.65  g.  N     1.02  g.  S 
of  which  is  eliminated — 

in  the  urine:           9.406  g.  C     2.663  g-  H  14.099  g.  O     16.28  g.  N     1.02  g.  S 

in  the  feces:            i-47i  g-  C    0.212  g.  H  0.889  g-  O      0.37  g.  N 
leaving  a  residuum  for  the  respiratory  process  of — 

41.50    g.  C     4.40    g.  H  7.69    g.  O 
deduct  intra- 
molecular water: 0.961 7.69 

41.50    g.  C     3.439  g-  H 

These  quantities  of  carbon  and  hydrogen  would  require 
138.18  grams  of  02  and  produce  152.17  grams  of  C02.  Since 
1  gram  of  oxygen  is  the  equivalent  of  0.699  liter  and  1  gram 
of  carbon  dioxid  amounts  to  0.5087  liter,  the  R.  Q.  would 
be  II 63  liters  of2  =  0.801.  From  these  data  it  may  be  calcu- 
lated that  for  every  gram  of  urinary  nitrogen  derived  from 
protein  8.45  grams  of  oxygen  are  required  for  the  oxidative 
process  and  9.35  grams  of  carbon  dioxid  are  eliminated  in 
virtue  of  such  oxidation. 

In  consequence  of  this,  one  may  estimate  the  substances 
oxidized  in  the  organism  by  deducting  from  the  total  elimina- 
tion of  carbon  dioxid  the  quantity  derived  from  protein 
(grams  urinary  N  X  9.35),  and  from  the  total  oxygen  absorbed 
that  required  to  oxidize  protein  (grams  urinary  N  X  8.45). 
From  the  figures  so  obtained  one  determines  the  non-protein 
R.  Q.  From  this  the  part  played  by  fat  and  carbohydrate  in 
metabolism  may  be  computed.  For  when  fat  alone  is  oxidized 
the  quotient  will  be  0.707,  and  when  carbohydrate  is  oxidized 
it  will  be  1. 00.  Quotients  which  are  intermediary  between 
these  two  indicate  that  mixtures  of  the  two  materials  are 
being  destroyed  (see  p.  61).  Knowing  the  quantities  of  these 
gases,  their  relative  volumes  (the  R.  Q.),  and  also  the  nitrogen 
elimination,  it  is  possible  to  calculate  exactly  what  amounts 

1  Loewy:   "Oppenheimer's  Handbuch  der  Biochemie,"  1911,  iv,  1,  279. 


THE    ATWATER-ROSA    RESPIRATION    CALORIMETER 


6l 


of  protein,  carbohydrate,  and  fat  have  been  oxidized  during 
the  period  of  experimentation. 

The  significance  of  the  Non-protein  Respiratory  Quotient  as  regards  the  heat 
value  of  i  liter  of  oxygen,  and  the  relative  quantity  in  calories  of  carbohydrate 
and  fat  consumed.     (Modified  from  Zuntz  and  Schumburg.) 


Calories  for  i  Liter  O2. 

R.  Q. 

Carbohydrate. 

Fat. 

Number. 

Logarithm. 

Per  Cent. 

Per  Cent. 

0.707 

4.686 

O.67080 

0 

100 

0.71 

4.690 

O.67116 

1.4 

98.6 

0.72 

4.702 

O.67231 

4.8 

95-2 

o.73 

4.714 

O.67346 

8.2 

91.8 

0.74 

4.727 

O.67460 

11.6 

88.4 

°-75 

4-739 

O.67574 

i5-o 

85.0 

0.76 

4-752 

O.67688 

18.4 

81.6 

0.77 

4.764 

O.67801 

21.8 

78.2 

0.78 

4.776 

O.67913 

25.2 

74-8 

0.79 

4.789 

O.68024 

28.6 

7i-4 

0.80 

4.801 

O.68136 

32.0 

68.0 

0.81 

4.813 

O.68247 

35-4 

64.6 

0.82 

4-825 

O.68358 

38.8 

61.2 

0.83 

4.838 

O.68469 

42.2 

57-8 

0.84 

4.850 

O.68578 

45-6 

54-4 

0.85 

4.863 

O.68690 

49 -o 

51.0 

0.86 

4.875 

O.68800 

52-4 

47.6 

0.87 

4.887 

O.68910 

55-8 

44.2 

0.88 

4.900 

O.69019 

59-2 

40.8 

0.89 

4.912 

O.69128 

62.6 

37-4 

0.90 

4.924 

O.69230 

66.0 

34-o 

0.91 

4-936 

0-69343 

69.4 

30.6 

0.92 

4.948 

O.69450 

72.8 

27.2 

o.93 

4.960 

O.69557 

76.2 

23.8 

0.94 

4-973 

■    O.69664 

79-6 

20.4 

o.95 

4-985 

O.69771 

83.0 

17.0 

0.96 

4-997 

O.69878 

86.4 

13.6 

0.97 

5.010 

O.69985 

89.8 

10.2 

0.98 

5.022 

O.70092 

93-2 

6.8 

0.99 

S-°34 

O.70199 

96.6 

3-4 

1. 00 

5-Q47 

O.70307 

100. 0 

0.0 

The  R.  Q.,  therefore,  ranges  from  0.707  for  fat  to  1.00  for 
carbohydrate.  Exceptions  may  be  noted  under  conditions 
involving  the  conversion  of  carbohydrate  into  fat  in  which 
case  the  quotient  exceeds  unity  (see  p.  306)  and  in  severe  dia- 
betes, when  the  quotient  may  be  less  than  0.707  (see  p.  470). 

From  this  analysis  of  the  oxidative  process  associated 
with  the  destruction  of  carbohydrate,  fat,  and  protein  in  the 


62 


SCIENCE    OF   NUTRITION 


organism,  it  is  possible  to  compute  the  heat  value  of  the  res- 
piratory gases  when  the  various  substances  are  oxidized. 
This  knowledge  may  be  compressed  into  the  following  table 
given  by  Loewy1: 


i  Gram 

O2 

ABSORBED. 

C02 

FORMED. 

R.Q. 

Calories. 

Calories. 

Substance. 

1  Liter  O2. 

1  Liter  CO2. 

Protein 

Fat 

Starch 

C.c. 

966.3 

2019.3 

828.8 

C.c. 

773-9 

1427-3 

828.8 

0.801 
0.707 
1. 000 

4.316 
9.461 

4.182 

4-485 
4.686 

5 -047 

5-579 
6.629 

5 -047 

Based  upon  the  analytic  figures  given  for  protein,  it  may 
be  computed  that: 

1  gram  urinary  nitrogen  =  26.51  calories. 

The  calories  derived  from  the  oxidation  of  fat  and  carbohy- 
drate given  by  Zuntz  and  Schumburg2  are  reproduced  on  p.61. 

An  example  of  the  calculation  of  indirect  calorimetry 
may  be  of  value  as  an  illustration.  The  subject  was  a  dog 
weighing  12.75  kilograms  and  the  period  was  one  hour  in 
duration.  The  calories  directly  determined  by  the  calorimeter 
are  also  given : 


co2 

Grams. 


O2      R.  Q.    Urine  N 
Grams.  Grams. 


Respiratory  exchange  6.75 

Deduct  protein  (0.136  X  9-35)  =  1-27 


6.17 
(0.136  X  8.45)  =  1. 15 


0.79     0.136 


Non-protein 


5-48 


5.02     0.79 
(=  3.51  liters) 


Calories 
Indirect. 


Calories 
Direct. 


Protein  calories  (0.136  grams  N  X  26.51)        =    3.60 
Non-protein  calories  (3.51  liters  O2  X  4.789*)  =  16.83 


*  Calorific  value  of  1  liter  O2  when  R.  Q. 


20.43  20.92 

Difference,  2.5  per  cent. 
0.79. 


The  same  method  is  employed  in  the  calculations  of  the 
metabolism  of  man. 

1  For  slightly  different  values  consult  Benedict  and  Talbot:   "The  Gaseous 
Metabolism  of  Infants,"  Carnegie  Institution,  Publication  201,  1914,  p.  26. 

2  Zuntz  and  Schumburg:   "Studien  zu  einer  Physiologie  des  Marsches," 
Berlin,  1901,  p.  361. 


THE   ATWATER-ROSA   RESPIRATION   CALORIMETER  63 

In  a  series  of  twenty-two  different  experiments  with  a  dog 
Murlin  and  Lusk1  obtained  the  following  results: 

Calories. 

Indirect  calorimetry 2244 

Direct  calorimetry 2230 

Difference 0.6  per  cent. 

In  fourteen  of  the  twenty-two  experiments  the  individual 
error  was  less  than  2  per  cent. 

The  following  is  a  description  of  the  principles  of  an 
Atwater-Rosa  respiration  calorimeter  with  the  improvements 
added  by  Benedict,2  Williams,3  and  others,  which  has  been 
adapted  for  the  use  of  patients  in  Bellevue  Hospital:4 

PRINCIPLE   OF   THE   ATWATER-ROSA-BENEDICT   RESPIRATION 
CALORIMETER6 

The  apparatus  is  divided  into  two  functional  parts,  one  for  measuring  the 
gaseous  exchange,  the  other  for  measuring  the  heat  production  of  the  subject. 
A  schematic  presentation  is  here  given  (Fig.  1). 

The  Gas  Analysis. — The  inner  lining  of  the  apparatus  presents  an  air-tight 
copper  box  having  a  capacity  of  11 23  liters.  One  end  of  the  box,  through 
which  the  patient  lying  on  the  bed  is  admitted,  may  be  closed  with  a  glass 
plate  by  means  of  wax.  The  air  within  the  box  is  purified  by  drawing  it  out 
of  an  opening  in  the  box  through  a  rubber  tube  and  forcing  it  by  means  of  a 
rotary  blower  through  a  system  of  absorbers,  whence  it  returns  again  to  the 
box  by  another  rubber  tube.  It  passes  (see  diagram)  first  through  sulphuric 
acid  (1),  which  removes  the  water,  then  through  moist  soda  lime  (2),  which 
removes  the  carbon  dioxid,  and  next  through  sulphuric  acid  (3),  which  absorbs 
the  moisture  taken  from  the  soda  lime.  If  the  bottles  be  previously  weighed, 
the  gain  in  weight  of  1  represents  water  absorbed,  and  the  gain  in  weight  of 
2  plus  3  equals  the  carbon  dioxid  absorbed.  By  this  method  the  water  and 
carbon  dioxid  produced  by  a  man  are  taken  from  the  air,  while  oxygen  within 
the  chamber  is  being  absorbed  by  the  man  himself.  This  causes  a  diminution 
in  the  volume  of  the  contents  of  the  box.  In  order  to  replace  the  oxygen  used, 
oxygen  is  automatically  fed  into  the  system  from  an  oxygen  cylinder  which 
may  be  weighed  before  and  after  the  period.  The  automatic  feeding  of  oxygen 
into  the  box  is  accomplished  by  means  of  a  spirometer  whose  interior  is  con- 
nected with  the  interior  of  the  calorimeter  chamber.     As  the  volume  of  the 

1  Murlin  and  Lusk:   "Jour,  of  Biological  Chemistry,"  1915,  xxii,  17. 

2  Benedict  and  Carpenter:  Carnegie  Institution  of  Washington,  1910,  Pub- 
lication 123. 

3  Williams:   "Jour,  of  Biological  Chemistry,"  191 2,  xii,  317. 

4  Riche  and  Soderstrom:    "Archives  of  Internal  Medicine,"  1915,  xv,  805. 
8  Lusk:   "Archives  of  Internal  Medicine,"  1915,  xv,  793. 


64 


SCIENCE    OF   NUTRITION 


Fig.    i. — Schematic  diagram  of  the  Atwater-Rosa-Benedict  respiration  ca- 
lorimeter. 


Ventilating  System: 

02,  Oxygen  introduced  as  consumed 
by  subject. 

3,  H2SO4  to  catch  moisture  given 
off  by  soda  lime. 

2,  Soda  lime  to  remove  CO2. 

1,  H2SO4  to  remove  moisture  given 
off  by  patient. 

Bl,  Blower  to  keep  air  in  circula- 
tion. 
Indirect  Calorimetry: 

Increase  in  weight  of  H2SO4  (1)  = 
water  elimination  of  subject. 

Increase  in  weight  of  soda  lime 
(2)  +  increase  in  weight  of 
H2SO4  (3)  =  CO2  elimination. 

Decrease  in  weight  of  oxygen  tank 
=  oxygen  consumption  of  subject. 
Heat-absorbing  System: 

A,  Thermometer  to  record  temper- 
ature of  ingoing  water. 

B,  Thermometer  to  record  temper- 
ature of  outgoing  water. 


V,  Vacuum  jacket. 

C,  Tank  for  weighing  water  which 
has  passed  through  calorimeter 
each  hour. 

W,  Thermometer  for  measuring 
temperature  of  wall. 

Ai,  Thermometer  for  measuring 
temperature  of  the  air. 

R,  Rectal  thermometer  for  measur- 
ing temperature  of  subject. 
Direct  Calorimetry: 

Average  difference  of  A  and  B  X 
liters  of  water  +  (gm.  water 
eliminated  X  0.586)  =±=  (change 
in  temperature  of  wall  X  hydro- 
thermal  equivalent  of  box)  ± 
(change  of  temperature  of  body 
X  hydrothermal  equivalent  of 
body)  =  total  calories  pro- 
duced. 
Th,  thermocouple;  Cu,  inner  copper 

wall;  CU2,  outer  copper  wall;  E,  F, 

dead  air-spaces. 


THE   ATWATER-ROSA   RESPIRATION   CALORIMETER  65 

air  in  the  box  decreases,  the  spirometer  falls  until  a  certain  point  is  reached, 
at  which  an  electric  contact  releases  a  clamp,  which  allows  oxygen  from  the 
oxygen  cylinder  to  enter  the  box,  causing  the  spirometer  to  rise,  break  its 
electric  contact,  and  clamp  off  the  oxygen  supply.  So  sensitive  is  the  spirom- 
eter to  the  movement  of  the  patient  that  a  device  called  a  "work  adder"  has 
been  attached  to  it,  which  records  the  subject's  movements. 

At  the  beginning  of  an  hourly  period  of  experimentation  an  observer  at 
the  table  calls  "time."  At  this  instant  the  rotary  blower  is  stopped,  the  air 
current  switched  so  as  to  pass  through  a  new  set  of  weighed  absorbers,  and 
then  the  rotary  blower  is  started  again.  At  the  word  "time"  an  operator  also 
turns  a  pet-cock  which  cuts  off  the  respiratory  chamber  from  the  spirometer 
cylinder,  which  is  then  filled,  always  to  a  given  point,  with  oxygen  from  the 
oxygen  cylinder.  The  pet-cock  is  now  opened  and  a  freshly  weighed  oxygen 
cylinder  is  placed  in  the  position  of  the  other,  which  is  removed.  Repeating 
these  procedures  an  hour  later,  one  may  determine  by  difference  in  weight  the 
gain  of  water  and  carbon  dioxid  by  the  absorbers  and  the  loss  of  oxygen  by 
the  cylinder.  The  figures  are  subject  to  corrections  due  to  (1)  gain  or  loss 
of  water  or  carbon  dioxid  content  in  the  box  itself  during  the  period,  which 
gain  or  loss  must  be  added  to  or  subtracted  from  the  increase  in  weight  of 
the  absorber  system.  This  gain  or  loss  of  water  and  carbon  dioxid  in  the  box 
also  affects  the  volume  of  the  air  in  the  box  and,  therefore,  the  quantity  of 
oxygen  admitted,  as  do,  in  addition  (2),  a  change  in  temperature  within  the 
box  and  (3)  a  change  in  barometric  pressure.  These  corrections  must  be 
made  in  order  to  determine  whether  oxygen  is  to  be  added  or  subtracted  from 
the  quantity  which  has  been  furnished  from  the  oxygen  cylinder.  The  result 
gives  the  quantity  of  oxygen  which  the  man  has  absorbed.  It  is  apparent  that 
all  the  errors  of  determination  fall  on  the  oxygen,  and  yet  the  exactness,  of 
the  method  is  witnessed  by  the  close  approximation  in  alcohol  check  experi- 
ments of  the  theoretic  and  actual  values  for  oxygen  consumed. 

If  a  person  in  the  calorimeter  moves  even  the  arm  during  the  critical 
moments  just  before  "time"  is  called,  the  increased  local  heating  of  the  air 
may  cause  the  spirometer  to  rise  to  a  considerable  height,  of  which  the  air 
thermometers  inside  the  box  fail  to  make  compensatory  record,  and  the  oxygen 
determination  will  be  too  low  in  that  hour  and  too  high  in  the  next. 

Analysis  of  the  air  in  the  interior  of  the  chamber  is  made  just  before  the 
beginning  of  each  hour  by  passing  10  liters  of  air  from  the  box  through  three 
U  tubes  containing,  respectively,  sulphuric  acid,  soda  lime,  and  sulphuric  acid, 
then  through  a  Bohr  gas-meter,  and  back  into  the  box  again.  This  is  called  the 
"residual  analysis." 

Under  the  conditions  present  in  the  respiration  apparatus  carbon  dioxid 
is  measured  with  the  greatest  ease  and  accuracy.  Oxygen  is  also  measured 
with  accuracy  if  the  person  within  the  box  lies  perfectly  quiet  for  ten  minutes 
before  the  end  of  the  period,  whereas  water  production  is  the  least  accurate 
of  all  the  determinations  on  account  of  the  varying  hygroscopic  condition  of 
the  walls,  bedding,  and  other  surfaces  within  the  closed  spaces  of  the  apparatus. 

The  Measurement  of  Heat  Produced. — Roughly  speaking,  one-quarter  of 
the  heat  eliminated  by  a  man  is  present  in  the  water  vapor  which  is  absorbed 
5 


66  SCIENCE    OF   NUTRITION 

by  the  first  sulphuric  acid  bottle  on  the  absorber  table.  At  200  C.  0.586 
calories  are  contained  as  latent  heat  in  1  gram  of  vaporized  water. 

The  rest  of  the  heat  loss  takes  place  by  radiation  and  conduction.  It  is 
this  heat  which  is  measured  by  the  calorimeter  itself.  The  mechanism  of 
the  calorimeter  is  essentially  twofold.  In  the  first  place,  there  is  no  heat  loss 
through  the  walls  of  the  apparatus,  and,  secondly,  the  heat  produced  by  a 
man  within  is  removed  from  the  chamber  by  a  current  of  cold  water  flowing 
through  copper  tubes  suspended  from  the  upper  wall  of  the  chamber.  If 
the  walls  allowed  no  heat  to  pass,  it  is  obvious  that  without  the  cooling  effect 
of  the  water-pipes  the  temperature  of  the  air  in  the  box  would  soon  attain 
the  temperature  of  the  human  body  instead  of  being  about  23°  C,  at  which  it 
is  usually  held.  The  apparatus  is  therefore  a  constant-temperature,  water- 
cooled  calorimeter.  It  is  evident  that  if  no  heat  is  allowed  to  pass  through  the 
walls  of  the  calorimeter,  then  the  heat  produced  within  the  chamber  will  be 
removed  in  the  current  of  cold  water  flowing  through  the  heat-absorbing  pipes 
inside  the  chamber  of  the  apparatus.  If  the  temperatures  of  the  ingoing  and 
of  the  outgoing  water  are  known  and  the  quantity  of  water  which  has  passed 
through  the  heat-absorber  during  an  hour  is  measured,  the  quantity  of  heat 
carried  away  in  the  current  of  water  can  be  accurately  determined.  For  ex- 
ample, if  the  difference  between  the  temperature  of  the  ingoing  and  outgoing 
water  is  2.50  degrees,  and  20  liters  of  water  have  passed  through  the  heat  ab- 
sorber in  one  hour,  then  50  calories  of  heat  have  been  carried  away  from  the 
apparatus  during  the  period.  If  the  temperature  of  the  walls  within  the  appa- 
ratus has  undergone  a  change  this  value  is  subject  to  corrections,  but  other- 
wise the  total  heat  elimination  of  the  person  is  measured  by  the  50  calories 
so  determined  plus  the  heat  value  of  water  vaporized  during  the  hour. 

To  obtain  an  even  flow  of  water  through  the  heat-absorber  the  water  is 
supplied  from  a  constant-level  tank  placed  above  the  calorimeter.  To  obtain 
ingoing  water  of  an  even  temperature  Williams  passed  the  previously  ice- 
cooled  water  current  through  a  Gouy  temperature  regulator  and  then  through 
a  current  regulator  designed  by  himself.  These  improvements  allow  the  in- 
going water  to  enter  the  calorimeter  at  a  temperature  which  may  not  vary 
more  than  0.020  C.  during  hours  of  experimentation  and,  for  the  first  time, 
permit  the  exact  measurement  of  small  quantities  of  heat  in  this  type  of 
apparatus.  The  temperatures  of  the  ingoing  and  outgoing  water  are  taken 
every  four  minutes  by  electric  resistance  thermometers  and  are  read  in  con- 
nection with  a  galvanometer  and  Kohlrausch  bridge  on  an  observer's  table. 
The  quantity  of  the  water-flow  is  determined  by  weighing;  the  water  is  diverted 
at  the  call  of  "time,"  so  that  the  exact  quantity  for  the  hour  is  collected  in  a 
previously  weighed  receptacle. 

Having  learned  how  the  heat  produced  within  the  apparatus  is  carried 
away,  the  problem  of  how  to  prevent  loss  of  heat  through  the  walls  of  the 
chamber  remains  to  be  discussed.  This  was  accomplished  through  a  device 
introduced  by  Rosa.  The  calorimeter  is  constructed  of  three  walls,  an  inner 
copper  wall  which  has  already  been  described  as  the  lining  of  the  respiration 
chamber,  an  outer  copper  wall  separated  from  the  inner  wall  by  a  space  of 
dead  air,  and  an  insulating  wall  (made  of  two  layers  of  "compo-board,"  the 


THE   ATWATER-ROSA   RESPIRATION   CALORIMETER  67 

space  between  them  being  filled  with  cork),  which  insulating  wall  is  separated 
from  the  outer  copper  wall  by  a  second  space  containing  dead  air.  It  is  ob- 
vious that  if  the  inner  and  outer  copper  walls  of  the  calorimeter  have  the  same 
temperature  there  will  be  no  exchange  of  heat  between  them.  Therefore, 
to  prevent  a  gain  or  loss  of  heat  by  the  inner  wall,  it  is  necessary  to  maintain 
the  outer  wall  always  at  exactly  the  same  temperature  as  the  inner  wall,  under 
which  circumstances  the  latter  cannot  gain  or  lose  heat  to  its  neighbor. 

In  order  to  detect  differences  in  temperature  between  the  outer  and  inner 
walls  Rosa  arranged  thermo-couples  in  series  between  the  two  walls.  In  this 
fashion  the  top,  sides,  and  bottom  of  the  box  are  successively  tested  every  four 
minutes  by  an  operator  at  the  observer's  table  to  determine  whether  there  is 
any  difference  in  temperature  between  the  outer  and  inner  walls.  If  the  outer 
wall  is  found  to  have  a  different  temperature  from  the  inner  wall,  its  tempera- 
ture is  brought  to  that  of  the  inner  wall  by  the  following  device:  A  cooling 
current  of  water  runs  through  pipes  between  the  insulating  and  outer  copper 
wall,  and  in  this  same  space,  along  the  line  of  the  pipes,  run  "Therlo"  resistance 
wires  carrying  an  electric  current  for  the  warming  of  this  interspace  (see  Fig.  2). 
By  varying  the  intensity  of  the  electric  currents  which  severally  supply  the 
spaces  to  top,  sides  and  bottom,  the  temperatifre  of  these  spaces  can  be  so 
controlled  as  to  heat  or  cool  the  outer  copper  wall  and  maintain  it  at  exactly 
the  same  temperature  as  the  inner  copper  wall.  This  is  the  effective  system 
which  prevents  a  loss  or  gain  of  heat  through  the  wall  of  the  calorimeter. 

Resistance  thermometers  are  attached  to  the  inner  walls  of  the  calorim- 
eter, and  if  the  temperature  of  the  walls  rises  or  falls  between  the  beginning 
and  end  of  the  experiment,  a  correction  must  be  made.  It  has  been  found 
that  19  calories  are  absorbed  by  the  Sage  calorimeter  when  the  inner  wall  rises 
1  degree.  Conversely,  19  calories  are  given  up  by  a  fall  of  1  degree.  This  is 
the  hydrothcrmal  equivalent  of  the  box. 

The  temperature  of  the  air  entering  the  box  from  the  absorbing  table  is 
always  heated  to  exactly  the  same  temperature  as  the  air  leaving  the  box. 

Finally,  an  electric  resistance  thermometer  inserted  10  or  12  cm.  into  the 
rectum  of  the  person  in  the  calorimeter  gives  information  regarding  the  reten- 
tion or  loss  of  heat  in  his  organism.  The  specific  heat  of  a  man  is  assumed  to 
be  0.83,  that  is  to  say,  0.83  calorie  raises  1  kilogram  1  degree.  If,  therefore, 
the  body  temperature  of  a  man  weighing  70  kilograms  rises  or  falls  1  degree, 
the  quantity  of  heat  lost  or  gained  by  the  body  will  be  70  X  0.83,  or  58.1 
calories.  This  is  on  the  assumption  that  the  rise  of  body  temperature  is 
everywhere  the  same  as  takes  place  in  the  rectum,  a  supposition  which,  un- 
fortunately, is  not  always  true  (see  p.  132). 

The  accompanying  scheme  (on  p.  68)  gives  the  details  regarding  the  em- 
ployment of  the  three  individuals  who  conduct  a  calorimeter  experiment. 

It  may  be  added  that  special  care  has  been  taken  to  make  the  appearance 
of  the  calorimeter  attractive  to  the  eye,  and  that  the  spirit  of  the  small  ward 
in  connection  with  the  calorimeter  work  has  been  such  that  the  patients  have 
considered  themselves  especially  fortunate  when  chosen  for  the  diversion 
offered  by  a  morning's  occupancy  of  the  apparatus. 


68 


SCIENCE    OF   NUTRITION 


Scheme  of  Employment  of  Observers  in  a  Calorimeter  Experiment 


Period  of 
Obser- 
vation. 


Observer  i,  at  Elec- 
tric Control  Table. 


Observer  2,  in  Charge 
of  Experiment. 


Observer  3,  Calculator. 


Eight  min- 
utes be- 
fore. 

Five  min- 
utes be- 
fore. 

Four  min- 
utes be- 
fore. 

One-half 
minute 
before. 

At  "Time." 


Imme- 
diately 

after 
"Time." 


Brings  walls  into  exact  ther- 
mal equilibrium. 


Takes  final  reading  of  air, 
walls,  and  rectal  temper- 
ature. 

Presses  button  which  di- 
verts stream  of  water 
from  weighing  tank. 


Starts  taking  readings 
every  four  minutes  of 
ingoing  and  outgoing 
water,  of  air.  walls, 
rectal,  and  surface  ther- 
mometers. Reads  and 
adjusts  temperature  of 
top,  sides,  and  bottom 
of  calorimeter,  of  the  in- 
going air  and  water 
every  four  minutes,  or 
oftener  if  necessary. 


Signals  subject  to  lie  ab- 
solutely quiet. 

Starts  kymograph  record 
of  movements  of  spirom- 
eter. 


Sets  barometer. 


Shuts  spirometer  off  from 
box.  Fills  to  standard 
level  from  oxygen  tank. 


Records  and  sets  work- 
adder.  Signals  to  subject 
that  he  may  move. 
Weighs  oxygen  tank  and 
connects  with  box  again. 
Weighs  sulphuric  and 
soda  lime  bottles.  Con- 
nects them  up  again  and 
tests  for  leaks.  During 
remainder  of  hour  counts 
pulse,  inspects  valves 
for  leaks,  adjusts  tem- 
perature of  room, 
watches  subject,  etc. 


Starts  passing  first  10-liter 
sample  of  residual  air 
through  U  tubes. 


Finishes    first    and    starts 
second  residual. 


Finishes  second  residual. 


Stops  ventilating  current  of 
air.  Turns  valve  to  pass 
air  _  through  newly 
weighed  absorbers. 
Starts  ventilating  cur- 
rent. 

Weighs  water  tank  which 
has  received  all  the  water 
from  the  heat  absorber 
during  the  past  hour.  Di- 
verts stream  of  water  to 
this  tank  again.  Records 
barometer.  Weighs  re- 
sidual.      Calculates     re- 

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CHAPTER  III 

STARVATION 

Nutrition  may  be  defined  as  the  sum  of  the  processes  con- 
cerned in  the  growth,  maintenance,  and  repair  of  the  living 
body  as  a  whole  or  of  its  constituent  organs. 

An  intelligent  basis  for  the  understanding  of  these  processes 
is  best  acquired  by  a  study  of  the  organism  when  it  is  living 
at  the  expense  of  materials  stored  within  itself,  as  it  does  in 
starvation. 

Starvation  or  hunger  is  the  deprivation  of  an  organism  of 
any  or  all  the  elements  necessary  to  its  nutrition.  Thus  when 
carbohydrates  and  fats  only  are  eaten,  protein  hunger  ensues. 
If  the  body  is  deprived  of  water  or  of  calcium,  thirst  or  calcium 
hunger,  as  the  case  may  be,  follows.  Complete  starvation 
occurs  when  all  the  required  elements  are  inadequate.  A  fast- 
ing dog  to  whom  no  food  or  drink  is  offered  does  not  undergo 
starvation  in  this  sense,  for  the  metabolized  tissue  furnishes 
enough  water  for  the  urine  and  respiration.  There  is  also  no 
water  hunger  in  a  dog  when  meat  is  ingested,  for  the  meat 
contains  enough  water  to  dissolve  the  end-products  of  its 
metabolism  in  the  urine.  Dogs  and  cats  have  no  sweat-glands 
in  the  skin  except  in  the  pads  of  their  feet.  They  therefore 
are  not  so  susceptible  to  water  hunger  as  is  man,  whose  body 
surface  is  constantly  losing  moisture. 

A  true  picture  of  water  hunger  is  presented  by  Straub,1  who 
gave  a  dog  dry  meat  powder  mixed  with  fat.  Under  these 
circumstances  water  is  withdrawn  from  the  tissues  to  dissolve 
the  urea  formed.  He  found  that  muscles  may  lose  20  per 
cent,  of  their  water  content  without  pathologic  manifesta- 

1  Straub:    "Zeitschrift  fiir  Biologie,"  1899,  xxxviii,  537. 

69 


70  SCIENCE    OF   NUTRITION 

tions,  although  withdrawal  of  water  somewhat  increased  the 
protein  metabolism.  The  experiment  could  not  be  carried  to 
the  point  of  death  from  thirst,  for  after  a  few  days  the  food 
was  regularly  vomited,  on  account  of  the  decreased  flow  of  the 
digestive  secretions  and  an  altered  condition  of  the  intestinal 
canal.  The  non-absorption  of  the  meat  powder  threw  the 
body  on  the  resources  of  its  own  tissue,  and  this  form  of 
starvation,  as  has  been  shown,  does  not  constitute  water 
hunger. 

Rubner1  finds  that  starving  pigeons  die  of  thirst  in  four  to 
five  days,  while  those  allowed  only  water  live  twelve  days. 
Water  hunger  is,  therefore,  more  quickly  fatal  than  starvation 
when  water  is  allowed.  Under  the  usual  conditions  of  so- 
called  starvation  experiments  water  is  freely  allowed,  so  that 
water  hunger  does  not  enter  as  a  factor  into  the  following 
discussion. 

If  water  be  available,  the  organism  obtains  the  energy 
necessary  for  its  continued  existence  from  the  destruction  of  its 
own  store  of  protein  and  fat.  After  a  variable  length  of  time 
the  organism  succumbs.  Exposure  to  cold  greatly  hastens 
the  end.  What  is  ordinarily  called  death  from  starvation  is 
often  really  death  from  exposure. 

BoldirefP  described  rhythmic  movements  occurring  in 
the  empty  stomach,  and  Cannon  and  Washburn3  have  called 
attention  to  the  intimate  association  of  these  contractions 
with  the  pangs  of  hunger.  The  subject  has  been  studied  in 
detail  by  Carlson4  in  observations  upon  a  boy  with  a  gastric 
fistula.  Twenty-four  hours  after  a  meal  the  stomach  exhibited 
two  types  of  rhythmic  movements:  (i)  relatively  feeble,  but 
continuous  contractions  at  the  rate  of  three  per  minute,  and  (2) 
relatively  strong  contractions  of  the  fundus,  the  true  hunger- 
pains.     The  amplitude  of  these  latter  contractions  shows  a 

1  Rubner:   v.  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1903,  p.  53. 

2  Boldireff :   "Archives  des  sciences  biologiques,"  1905,  xi,  1. 

3  Cannon  and  Washburn:  "  American  Journal  of  Physiology,"  1911-12,  xxix, 

4  Carlson:   "American  Journal  of  Physiology,     1912-13,  xxxi,  151. 


STARVATION  7 1 

close  correspondence  with  the  intensity  of  the  sense  of  hunger 
simultaneously  registered.  During  strong  contractions  the 
knee-jerk  was  found  to  be  exaggerated,  indicating  an  increased 
tonus  of  the  nervous  system,  and  there  was  a  great  instability 
of  vasomotor  tone.  Carlson  suggests  that  this  close  asso- 
ciation of  the  hunger-pains  with  the  vasomotor  center  may  be 
the  cause  of  the  faintness  occurring  in  starvation.  The 
hunger  contractions  and,  in  consequence,  the  hunger  pangs  are 
inhibited  by:  (i)  the  stimulation  of  the  gustatory  nerves 
through  sweet,  bitter,  salt,  and  acid  substances;  (2)  chewing 
any  kind  of  substance,  be  it  well  or  ill  flavored  or  tasteless;  (3) 
smoking;  (4)  swallowing  movements.  Water,  coffee,  tea,  beer, 
wine,  and  brandy  when  taken  into  the  stomach  inhibit  the 
movements  and  relieve  the  sense  of  hunger,  though  water  is 
least  effective  in  this  regard. 

Succi  has  fasted  several  times  for  thirty  days.  Dr. 
Tanner,  an  American  physician,  for  forty  days;  and  Merlatti, 
in  Paris,  for  fifty  days.  Succi  took  laudanum  in  considerable 
quantity  to  stay  the  pain  in  his  stomach,  while  Merlatti  took 
only  water.1  The  effect  of  fasting  on  the  spirits  of  the  faster 
varies  with  the  individual.  Usually  there  is  a  loss  of  buoyancy 
of  spirit,  a  decreased  desire  to  work,  and  a  decrease  in  the 
actual  power  of  working.  Succi,  however,  was  capable  of 
considerable  exertion,  such  as  walking  and  riding,  without  ill 
effects.  A  dog  does  not  manifest  the  same  depression  as  is 
seen  in  man.  Dogs  may  be  starved  several  days  before  they 
are  run  in  a  hunt.  One  of  the  longest  fasts  on  record  is  that 
of  Kumagawa's2  dog,  which  died  on  the  ninety-eighth  day. 
This  dog  was  reduced  in  weight  from  17  to  5.96  kilograms,  a 
loss  of  65  per  cent. 

A  yet  longer  fast  has  been  reported  by  Hawk,3  in  which  a 
dog  fasted  from  February  6th  to  June  2d,  a  period  of  117  days, 
700  grams  of  water  having  been  administered  daily.     The 

1  Luciani:   "Das  Hungern,"  1890,  p.  28. 

2  Kumagawa  and  Miura:   "Archiv  fur  Physiologie,"  1898,  p.  431. 

3  Howe,  Mattill,  and  Hawk:  "Journal  of  Biological  Chemistry,"  1912,  xi, 
103. 


72  SCIENCE    OF   NUTRITION 

dog  remained  in  "good  spirits"  during  the  whole  fast,  although 
its  weight  fell  from  26.3  to  9.76  kilograms.  There  was  no 
indication  of  a  "premortal  rise"  in  the  nitrogen  elimination 
in  the  urine.  During  the  first  four  days  of  fasting  the  average 
nitrogen  elimination  in  the  urine  was  6.23  grams  or  0.23  gram 
per  kilogram  of  body  weight,  and  during  the  last  four  days  it 
averaged  2.44  grams  or  0.23  gram  per  kilogram.  The  dog 
then  passed  the  summer  upon  a  Kansas  farm,  fully  regained  his 
former  weight,  and  in  the  autumn  was  reported  to  be  in  better 
physical  condition  than  at  the  commencement  of  his  fast. 
A  second  or  "repeated  fast"  was  then  initiated  which  lasted 
104  days  with  no  harmful  results. 

The  day  to  day  history  of  the  starving  organism  must  now 
be  considered. 

In  the  first  days  the  amount  of  protein  metabolized  depends 
upon  the  two  factors,  the  glycogen  content  of  the  individual 
and  the  quantity  of  protein  ingested  before  the  starvation 
period.  The  influence  of  the  first  factor  was  shown  by 
Prausnitz.1  Fifteen  individuals  (mostly  medical  students  who 
were  taking  a  course  of  instruction  in  the  laboratory)  fasted 
for  sixty  hours.  The  first  day's  urine  was  collected  beginning 
after  twelve  hours  of  fasting.  The  second  day's  urine  con- 
tained in  12  cases  more  nitrogen  than  that  of  the  first  day  of 
starvation.  The  lower  protein  destruction  on  the  first  starva- 
tion day  must  have  been  due  to  the  continued  use  of  sugar 
from  the  glycogen  supply.  It  is  known  that  the  combustion  of 
sugar  considerably  reduces  the  protein  metabolism,  so  the 
second  day  and  not  the  first  of  starvation  should  be  taken  as 
the  basis  of  the  fasting  protein  metabolism. 

This  influence  of  glycogen  metabolism  on  that  of  protein 
during  the  first  and  second  days  of  fasting  is  beautifully  shown 
in  experiments  by  Benedict2  (see  also  p.  89). 

1  Prausnitz:   "Zeitschrift  fur  Biologie,"  1892,  xxix,  151. 

2  Benedict:  "The  Influence  of  Inanition  on  Metabolism,"  Carnegie  Insti- 
tution of  Washington,  1907,  Bulletin  No.  77. 


STARVATION 


73 


INFLUENCE  OF  GLYCOGEN  METABOLISM  ON  THAT  OF  PROTEIN 
IN   FASTING.     WEIGHTS  IN   GRAMS 


First  Day. 

Second  Day. 

Individual, 

Glycogen 
Metabolized. 

N 
Elimi- 
nated. 

Glycogen 
Metabolized. 

N 
Elimi- 

Total. 

Per  Kg. 

Total. 

Per  Kg. 

nated  . 

S.  A.  B 

S.  A.  B 

S.  A.  B 

H.  C.  K 

H.  R.  D '.... 

181.6 

135-3 

64.9 

165.6 

32.8 

3-15 
2.31 
1.09 

2-33 
0-59 

5-84 
10.29 
12.24 

9-39 

13-25 

29.7 
18.1 
23.1 

44-7 
41.6 

O.52 
O.31 

o-39 
0.64 
0.76 

11.04 
11.97 

12.45 
14.36 

13-53 

It  is  evident  that  where  there  is  an  abundant  glycogen  re- 
serve the  protein  metabolism  is  reduced  by  the  oxidation  of 
carbohydrates,  but  where  there  is  little  glycogen  to  draw  upon 
the  protein  metabolism  is  high  even  on  the  first  day  of  starva- 
tion. 

The  second  factor,  or  the  influence  of  the  previous  meat  in- 
gestion, is  especially  dominant  in  dogs.  (For  effect  on  man 
see  p.  275.)  Voit1  fed  a  dog  weighing  35  kilograms  with 
different  quantities  of  meat  and  noticed  the  effect  on  urea 
elimination  during  subsequent  starvation.  The  results  were 
as  follows: 

INFLUENCE    OF    PREVIOUS    DIET    ON    UREA    ELIMINATION   IN 

STARVATION 


Last  food  day. . . 

1  st  fasting  day. 

2d      " 

3d      " 

4th     " 

5th     " 

6th     " 

7th     " 

8th     " 

9th     " 
10th     " 


Grams  of  Urea  Excreted  During  Starvation 
Following  Various  Diets. 


Meat, 
2500  G. 


180.8 
60.I 
24.9 
19. 1 

17-3 
12.3 

13-3 
12.5 
10. 1 


Meat, 

1800    G.; 

Fat,  250  G. 


30.0 

no. 

37-5 

29. 

23-3 

18. 

16.7 

17- 

14.8 

14. 

12.6 

14. 

12.8 

13- 

12.0 

12. 

12. 

Meat, 
1500  G. 


Meat, 
1500  G. 


110.8 
26.5 
18.6 

15-7 
14.9 
14.8 
12.8 
12.9 
12. 1 
11.9 
11.4 


Bread. 


24.7 
19.6 
15.6 
14.9 
13.2 
12.7 
13.O 


1  Voit:   "Zeitschrift  fur  Biologie,"  1866,  ii,  307. 


74 


SCIENCE   OF   NUTRITION 


It  is  evident  from  this  that  on  the  sixth  day  of  starvation 
the  urea  elimination  was  the  same  in  all  cases,  or  about  13 
grams  of  urea  per  day.  Voit  deducted  the  12  grams  from 
what  he  had  found  for  the  first  days  and  obtained  the 
grams  of  urea  which  were  derived  from  the  previous  food, 
as  follows: 


UREA     ELIMINATION     IN     STARVATION     ATTRIBUTABLE     TO 
PREVIOUS   DIET 


(Last  food  day) . 

1st  fasting  day. . 

2d 

3d        " 

4th 

5th       " 


Meat, 
1500  G. 


(168.8) 


12.9 


5-3 
o-3 


Meat, 

1800  G.; 

Fat,  250  G. 


(118.0) 

25-5 

n-3 

4-7 

2.8 

0.6 


Meat, 
1500  G. 


Meat, 
1500  G. 


14-5 
6.6 

3-7 
2.9 
2.8 


Bread. 


(12.7) 
7.6 
3-6 
2.9 
1.2 
0.7 


The  amount  of  extra  protein  metabolism  is  seen  from  the 
above  to  be  directly  dependent  on  the  previous  feeding,  a 
common  level  being  reached  in  all  cases  on  the  fifth  day  of 
fasting. 

These  experiments  led  Voit  to  differentiate  between  "cir- 
culating protein,"  which  could  be  absorbed,  carried  to  the 
tissues,  and  burned,  and  "organized  protein,"  the  more  re- 
sistant living  protein  of  the  tissues  themselves.  Voit1  stated 
that  in  metabolism  the  lifeless  protein  furnished  to  the  cells  by 
the  blood  was  used  in  preference  to  the  living  organized  tissue 
protein.  He  quoted  Landois'  experiments,  which  show  that 
after  producing  an  artificial  plethora  through  injection  of 
blood,  the  serum  proteins  are  readily  burned  and  their  nitrogen 
eliminated  in  the  urine,  while  the  red  blood-cells  containing  the 
organized  protein  are  only  slowly  destroyed.  If  serum  alone 
be  transfused,  its  protein  is  rapidly  destroyed.2 


1  Voit:   "Handbuch  der  Ernahrung,"  1881,  p.  300. 

2  Forster:   "Zeitschrift  fur  Biologie,"  1875,  xi,  496. 


STARVATION  75 

Even  in  starvation  there  is  evidence  of  "circulating  protein" 
as  food  for  the  tissues.  Thus  Miescher  showed  that  the 
salmon,  after  entering  the  Rhine  from  the  sea,  virtually 
starves.  Yet  the  genital  organs  of  both  male  and  female 
develop  greatly,  this  being  at  the  expense  of  the  muscles, 
which  may  lose  55  per  cent,  of  their  weight.  This  protein 
must  have  been  carried  to  the  various  parts  of  the  body  in 
the  circulating  blood-stream.  Miescher  finds  no  indication 
of  any  destruction  of  muscle-fibers  in  this  process  of  emaciation 
(see  p.  249).  It  is  interesting  in  this  connection  to  note  that 
A.  R.  Mandel1  has  been  able  at  a  pressure  of  300  to  350 
atmospheres  acting  on  lean  meat  seventy-two  hours  old  to 
press  out  a  fluid  containing  44  per  cent,  of  the  protein  present 
in  the  fibers,  and  this  without  visible  change  from  the  normal 
histologic  appearance  of  the  muscle. 

It  seemed  quite  possible  that  in  ordinary  starvation  protein 
from  muscle  and  other  tissues  passed  to  the  blood  and  was 
carried  to  all  the  organs  as  circulating  protein  for  the  nutrition 
of  their  cells. 

The  great  work  of  Kossel,  Hofmeister,  and  Emil  Fischer 
has  taught  that  the  essential  composition  of  protein  is  a 
structure  formed  of  chains  of  amino-acids.  Fischer  has  con- 
structed artificial  peptids,  bodies  in  which  two  or  more 
amino-acids  are  united  together.  For  example,  glycyl-glycin 
is  formed  by  the  union  of  two  molecules  of  glycocoll  with  the 
loss  of  water,  as  follows: 

H,NCH,COOH  H2NCH2CO 

— H20  =  I 

H2NXH2COOH  HNCH2COOH 

Glycocoll.  Glycyl-glycin. 

Fischer  has  hung  together  eighteen  of  these  radicles  in 
an  octodecapeptid  containing  four  leucin  and  fourteen  glyco- 
coll molecules  and  being  1-leucyl-triglycyl-l-leucyl-triglycyl-l- 
leucyl-octoglycy  1-gly  cin . 

1  Mandel:   Unpublished  work  from  the  Munich  Clinic  of  Prof.  Fr.  Midler. 


76  SCIENCE   OF   NUTRITION 

£JJ3NcHCH2CHNH2CO  1-leucyl 

CH2NHCO 

/ 
CH2NHCO  tri-glycyl 

/ 
CH2NHCO 

iN>CHCH2CH  NHCO  1-leucyl 

CH2NHCO 

/ 
CH2NHCO  tri-glycyl 

CH2NHCO 


CH 
CH 


^^CHCH2CH  NHCO  1-leucyl 

CH2NHCO 

/ 
CH2NHCO 

/ 
CH2NHCO 

/ 
CH2NHCO  octo-glycyl 

CH2NHCO 

/ 
CH2NHCO 

/ 
CH2NHCO 

/ 
CH2NHCO 

/ 
CH2NHCOOH  glycin 

N  =  20.8  per  cent. 

This  forms  a  body  akin  to  pepton.  The  high  molecular 
complexes  called  proteins,  which  constitute  the  basis  of  our 
being,  are,  after  all,  separable  into  simple  chemical  compounds. 
In  the  larger  molecule  these  amino-acids  are  chained  together, 
even  as  in  structural  framework  various  iron  beams  are 
riveted  together.  Digestive  proteolysis  or  internal  metabolism 
rends  the  higher  structure  of  the  molecule  and  leaves  its 
individual  supports,  the  amino-acids,  open  for  further  dis- 
integration.1 

The  various  proteins  differ  from  one  another  in  the  rela- 
tive quantity  of  the  different  amino-acids  which  they  contain, 

1  For  further  details  see  Plimmer:  "The  Chemical  Constitution  of  the 
Proteins,"  1908. 


STARVATION 


77 


and  also  undoubtedly  in  the  manner  of  chemical  linkage  of 
those  acids.  Thus  Abderhalden  has  called  attention  to  the 
fact  that  if  the  seventeen  different  chemical  units  be  joined  to- 
gether in  different  ways,  350,000,000  times  1,000,000  different 
combinations  are  possible  even  though  only  a  single  representa- 
tive of  each  unit  is  used.  In  this  manner  the  amino-acids  may 
form  combinations  the  possible  multiplicity  of  which  re- 
calls the  number  of  words  in  the  dictionary  formed  from  the 
letters  of  the  alphabet. 

The  following  table  presents  analytic  data  showing  the 
approximate  amounts  of  the  different  amino-acids  contained 
in  well-known  varieties  of  vegetable  and  animal  proteins: 


COMPARATIVE   COMPOSITION  OF  PROTEINS 


Amino-acids. 


Glycocoll 

Alanin 

Valin 

Leucin 

Prolin 

Phenylalanin. . . 
Aspartic  acid. . . 
Glutaminic  acid 

Serin 

Tyrosin 

Cystin 

Histidin 

Arginin 

Lysin 

Tryptophan. . . . 
Ammonia 


Zein 

(Maize). 


Per  cent. 

13-39 
1.88 

19-55 
9.04 

6-55 

1. 71 

26.17 

1.02 

3-55 
? 

0.82 

i-55 


3-64 


88.87 


Gliadin 

(Wheat). 


Per  cent. 


3-34 

6.62 

13.22 

2-35 

0.58 

43.66 

0.13 
1.50 

o.45 
1.84 
2.84 

0-93 
1. 00 

5-22 


85.68 


Casein 
(Milk). 


Per  cent. 

1-5° 
7.20 

9-35 

6.70 
3.20 
i-39 
15-55 
0.50 

4-5° 
? 

2.50 

3.81 

7.61 

1.50 

1.61 


66.9; 


Lactal- 

BtTMTN 

(Milk). 


Per  cent. 

2.50 
O.90 

19.40 
4.00 
2.40 
1.00 

IO.IO 
? 

2.20 
? 

2.06 

3-23 
0.16 

'+ 
1.32 


58.27 


Edestin 
(Hemp 
Seed). 


Per  cent. 
3.80 
3.60 
6.20 

14.50 
4.10 
3-09 
4-5° 

18.74 
o.33 
2.13 
1. 00 
2.19 

14.17 
1.65 
+ 
2.28 


82.28 


Ox 

Muscle.2 


Per  cent. 
4.0 
8.1 
2.0 

14-3 
8.0 

4-5 
10.6 

22.3 
? 

4.4 

? 

4-5 

n-5 

7.6 

+ 
1.07 


102.87 


Concerning  the  crystalline  vegetable  proteins  which  he  has 
investigated  Osborne3  writes:  "It  is  possible  to  establish  a 

Osborne,  T.  B.,  and  Mendel,  L.  B.:  "Journal  Biological  Chemistry," 
19 14,  xvii,  336,  modified  as  to  the  arginin,  histidin,  and  lysin  content  of  gliadin 
and  lactalbumin  to  accord  with  Osborne,  Van  Slyke,  Leavenworth,  and  Vino- 
grad,  Ibid.,  1915,  xxii,  259. 

2  Osborne  and  Jones:  "American  Journal  Physiology,"  1909,  xxiv,  437, 
modified  by  the  findings  of  Osborne  and  Jones,  Ibid.,  1910,  xxvi,  305. 

3  Osborne:   "Science,"  1908,  xxviii,  417. 


78  SCIENCE   OF   NUTRITION 

constancy  of  properties  and  ultimate  composition  between 
successive  fractional  precipitations  which  give  no  reason  for 
believing  the  substance  to  be  a  mixture  of  two  or  more  in- 
dividuals. On  chemical  grounds  there  is  no  more  reason  for 
dividing  the  proteins  into  two  groups  of  animal  and  vegetable 
proteins  than  there  is  in  making  a  similar  distinction  between 
the  carbohydrates.  Of  twenty-three  seed  proteins  which  have 
been  hydrolized,  all  have  yielded  leucin,  prolin,  phenylalanin, 
aspartic  acid,  glutamic  acid,  tyrosin,  histidin,  arginin,  and 
ammonia.  Glycocoll,  lysin,  and  tryptophan  are  the  only 
amino-acids  which  have  been  proved  lacking  in  any  one  of 
these  proteins." 

Osborne  and  Abderhalden  are  agreed  that  the  chemical 
constituents  of  protein  are  probably  all  known,  and  that  the 
usual  deficit  found  on  their  analysis  is  due  to  the  inadequacy 
of  the  methods  employed.  Thus  Osborne  and  Jones  found 
that  they  recovered  varying  percentages  of  different  amino- 
acids  when  a  mixture  of  known  quantities  was  analyzed.  If 
one  computes  their  analysis  of  ox  muscle  protein  on  the  basis 
of  analytic  losses  similar  to  those  found  when  the  mixture  of 
known  quantities  of  amino-acids  was  analyzed,  one  obtains 
nearly  103  per  cent,  of  the  value  of  the  original  ox  protein. 
This  value  includes  the  water  added  by  hydrolysis  in  the  break 
up  of  the  molecule. 

Osborne  finds  that  the  quantity  of  ammonia  liberated  in 
hydrolysis  bears  a  constant  relation  to  the  amount  of  glutamic 
and  aspartic  acids  recovered.  He  concludes  that  one  of  the 
carboxyl  groups  (COOH)  exists  as  an  amid  (CONH)2,  and 
that  in  reality  glutamin  and  asparagin  are  present  in  the  mole- 
cule, and  become  the  sources  of  ammonia  when  the  molecule 
is  broken. 

The  physiology  of  protein  metabolism  has  become  in  late 
years  the  physiology  of  the  amino-acids.  When  once  so 
regarded,  the  problem  is  one  of  the  study  of  the  behavior 
within  the  body  of  chemical  entities  which  can  be  prepared  in 
pure  crystalline  form  and  the  formulas  of  which  are  definitely 


STARVATION  79 

known.  The  fate  of  these  individual  amino-acids  will  be 
considered  at  another  time  (see  p.  184).  It  is  sufficient  to 
state  here  that  the  cleavage  of  protein  into  amino-acids 
through  digestion  hydrolysis  is  accomplished  without  the 
liberation  of  an  appreciable  quantity  of  heat,1  that  the  re- 
sulting amino-acids  are  absorbed  directly  into  the  blood- 
stream, and  that  in  so  far  as  they  are  reconstructed  into  new 
protein  within  the  organism  the  process  takes  place  without 
any  measurable  thermodynamic  reaction  (see  p.  245).  Since 
the  protein  content  of  blood-plasma  is  nearly  the  same  in 
fasting  as  after  large  ingestion  of  meat,  it  is  evident  that  the 
storage  of  such  ingested  protein  must  be  effected  elsewhere 
than  in  the  blood. 

A  preliminary  survey  of  the  more  recently  discovered 
information  regarding  the  interplay  between  the  proteins  and 
the  amino-acids  of  the  organism  may  be  of  service  at  this 
juncture.  The  absorption  of  amino-acids  by  the  blood  was 
first  indicated  by  the  work  of  Howell,2  who  dialyzed  dog's 
blood  both  before  and  after  giving  meat,  and  in  the  latter 
instance  recovered  more  material  on  adding  naphthylsulpho- 
chlorid  to  the  diffusate  than  in  the  former.  The  precipitate, 
however,  was  an  oil  and  its  quantity  could  not  be  measured  ac- 
curately. Folin  and  Denis3  introduced  glycocoll  or  alanin  into 
the  small  intestines  of  cats,  and  on  analyzing  the  blood  and 
muscle  tissue  noticed  a  large  increase  in  the  quantity  of 
"residual  nitrogen"  which  was  obtained  by  subtracting  "urea 
nitrogen"  from  "total  non-protein  nitrogen."  The  increase 
was  so  great  that  it  could  only  have  been  caused  by  the  influx 
of  the  amino-acids  themselves.  An  hour  after  the  introduction 
of  the  amino-acids  urea  appeared  in  increased  quantity  in  the 
blood.  Their  results  indicate  that  absorbed  amino-acids 
circulate  in  the  blood,  are  retained  in  the  muscle  tissue,  and 
that  after  an  hour  urea  rises  in  the  blood  in  response  to  the 

1  Hari:   "Pfliiger's  Archiv,"  1906,  cxv,  11. 

2  Howell,  W.  H.:    "American  Journal  of  Physiology,"  1906,  xvii,  273. 

3  Folin  and  Denis:  "Journal  of  Biological  Chemistry,"  1912,  xii,  141,  and 
previous  papers. 


80  SCIENCE   OF   NUTRITION 

increased  production  of  urea  in  the  tissues.  They  found  no 
increase  in  the  quantity  of  urea  or  of  ammonia  in  the  blood 
of  the  portal  vein  after  introducing  glycocoll  or  alanin  into  a 
loop  of  the  intestine,  and  by  this  experiment  demonstrated 
that  the  amino-acids  were  absorbed  unchanged  without 
deamination,  which  would  have  involved  ammonia  or  urea 
production. 

Van  Slyke  and  Meyer1  were  able  to  determine  directly 
amino-acids  in  the  blood.  Thus  the  absorption  of  12  grams 
of  glycocoll  from  the  intestine  of  a  dog  caused  an  increase  in 
the  amino-acid  content  of  the  blood  from  3.9  to  6.3  milligrams 
per  100  c.c.  of  blood  volume.  After  giving  1000  grams  of 
meat  to  a  dog  the  amino-acid  content  of  the  blood  doubled  or 
more  than  doubled  in  a  mesenteric  vein,  and  the  urea  content 
also  increased.  There  was  almost  as  great  an  increase  in  the 
amino-acid  content  of  the  femoral  vein  as  in  the  mesenteric, 
and  therefore  Van  Slyke  concludes  that  amino-acids  are  not 
largely  retained  by  the  liver. 

Van  Slyke  and  Meyer2  have  confirmed  the  work  of  Folin 
and  Denis  in  showing  that  the  tissues  absorb  amino-acids 
with  great  avidity.  The  normal  concentration  of  amino- 
acids  in  the  tissues  were  found  to  be  five  to  ten  times  that  in 
the  blood.  Optimal  figures  are  given  as  80  milligrams  per 
100  grams  of  muscle,  and  150  milligrams  per  100  grams  of 
liver.  In  one  experiment  the  introduction  into  the  vein  of  a 
dog  of  amino-acids  derived  from  casein  and  containing  4.06 
grams  of  nitrogen  resulted  after  half  an  hour  in  an  increase 
of  amino-acids  in  the  blood  from  3.9  to  45.4  milligrams  per 
100  grams.  This  quantity  would  account  for  5  per  cent,  of 
the  total  amount  injected,  and  since  1 1  per  cent,  was  elimi- 
nated in  the  urine  it  appears  that  the  remainder  or  3.41  grams 
of  N  must  have  been  absorbed  by  the  tissues. 

Finally,  it  was  shown  by  Van  Slyke  and  Meyer3  and  in- 
dependently by  Wishart4  that  although  the  ingestion  of  meat 

1  Van  Slyke  and  Meyer:  "Journal  of  Biological  Chemistry,"  191 2,  xii,  399. 

2  Ibid.,  1913-14,  xvi,  197.  3  Ibid.,  1913-14,  xvi,  231. 
4  Wishart:  "Journal  of  Biological  Chemistry,"  1915,  xx,  535. 


STARVATION  8 1 

in  large  quantity  increases  the  amino-acid  content  of  the  blood, 
it  does  not  increase  that  of  muscle  tissue.  It  is  therefore 
probable  that  when  nitrogen  is  retained  in  the  organism  it  is 
not  to  an  appreciable  extent  stored  as  digestion  products,  but 
rather  in  the  form  of  protein  (see  p.  169).  Such  amino-acids 
as  are  not  so  synthesized  are,  therefore,  destroyed  as  rapidly 
as  they  accumulate. 

Van  Slyke  and  Meyer1  conclude  that  absorbed  amino- 
acids  disappear  rapidly  from  the  liver,  although  their  con- 
centration in  the  muscle  suffers  no  appreciable  fall.  The 
urea  concentration  in  the  blood  increases.  The  liver  de- 
saturates  itself  and  in  this  way  metabolizes  superfluous 
protein. 

On  the  other  hand,  Fiske  and  Sumner,2  in  Folin's  labora- 
tory, after  tying  a  ligature  around  the  portal  vein  and  hepatic 
artery  of  a  dog,  find  that  intravenous  injection  of  amino-acids 
leads  to  as  great  a  formation  of  urea  as  in  a  normal  animal. 
They  explain  Van  Slyke's  results  as  indicating  that  the  liver 
might  rid  itself  of  amino-acids  as  it  does  of  glycogen  without 
being  of  necessity  involved  in  their  destruction. 

In  this  relation  it  may  be  added  that  Abderhalden3  showed 
several  years  ago  that  tryptophan  was  converted  into  kynu- 
renic  acid  as  readily  in  a  dog  with  an  Eck  fistula  (see  p.  451) 
as  in  one  without. 

The  first  actual  isolation  of  an  amino-acid  from  blood 
was  reported  by  Abel4  at  the  International  Physiological 
Congress  held  at  Groningen  in  the  summer  of  19 13.  Alanin 
was  found  in  considerable  amount  in  a  diffusate  formed  by 
dialyzing  the  blood  during  its  continuous  passage  from  an 
artery  of  a  living  animal  through  a  system  of  tubes  made  of 

1  Van  Slyke  and  Meyer:  "Journal  of  Biological  Chemistry,"  1913-14, 
xvi,  213. 

2  Fiske  and  Sumner:    "Journal  of  Biological  Chemistry,"  1914,  xviii,  285. 

3  Abderhalden,  London,  and  Pincussohn:  "Zeitschrift  fur  physiologische 
Chemie,"  1909,  lxii,  139.  Consult  also  Mathews  and  Nelson:  "Journal  of  Bio- 
logical Chemistry,"  1914,  xix,  229;  Taylor  and  Lewis:    Ibid.,  1915,  xxii,  77. 

4  Abel,  Rowntree,  and  Turner:  "Journal  of  Pharmacology  and  Experimental 
Therapeutics,"  1913-14,  v,  611. 

6 


82  SCIENCE    OF   NUTRITION 

celloidin  immersed  in  a  saline  solution,  the  blood  then  re- 
turning to  the  animal  by  a  vein.  This  method  of  vividiffusion 
yields  alanin  in  crystalline  form.  Histidin  and  creatinin 
may  be  determined  by  color  reactions.  Sugar,  urea,  am- 
monia /3-oxybutyric  acid,  and  lactic  acid  also  diffuse  from  the 
blood  in  marked  amounts. 

Abderhalden1  worked  with  50  and  100  liters  of  blood- 
serum  and  reports  the  presence  of  ten  different  amino-acids. 
Abel2  calls  attention  to  the  fact  that  secondary  changes  which 
may  conceivably  take  place  in  shed  and  coagulated  blood 
play  no  part  in  his  method  of  vividiffusion,  which  separates 
diffusible  substances  from  the  circulating  blood  of  living 
animals. 

Van  Slyke  and  Meyer3  report  that  free  amino-acids  do 
not  disappear  from  the  tissues  on  fasting,  but,  if  anything, 
they  tend  to  increase  there. 

These  facts  are  interpretative  of  conditions  in  fasting. 
That  amino-acids  are  produced  in  fasting  is  demonstrated  in 
the  cited  instance  of  the  salmon  in  which  the  protein  of  the 
genital  organs  increases  at  the  expense  of  muscle  protein. 
Thus  Kossel4  estimates  that  a  salmon  weighing  9  kilograms 
deposits  at  breeding  time  in  its  testicles  27  grams  of  salmin 
containing  22.8  grams  of  arginin.  Kossel  calculates  that 
metabolism  of  muscle  protein  during  this  time  yields  ample 
arginin  to  form  the  new  salmin. 

Other  evidence  of  the  constant  production  of  amino-acids 
in  the  tissues  in  fasting  is  offered  by  the  experiments  of  Turner, 
Marshall,  and  Lamson.5  In  these  important  investigations 
one-third  the  blood  of  a  dog  was  withdrawn,  the  blood  cor- 
puscles were  washed  with  normal  saline,  and  then  the  washed 
corpuscles  were  returned  to  the  body.     This  process  is  called 

1  Abderhalden :    "Zeitschrift  f.  physiolog.  Chem.,"  1913,  lxxxviii,  478. 

2  Abel:    First  Mellon  Lecture,  University  of  Pittsburgh,  1915,  p.  22. 

3  Van  Slyke  and  Meyer:  "Journal  of  Biological  Chemistry,"  1913-14.  xvir 
231. 

4  Kossel:  " Biochemisches  Zentralblatt,"  1906,  v,  ^^. 

6  Turner,  Marshall  and  Lamson:  "Journal  of  Pharmacology  and  Experi- 
mental Therapeutics,"  1915,  vii,  129. 


STARVATION 


83 


by  Abel  plasmapheresis.  Three  such  bleedings,  with  the  re- 
turn of  the  corpuscles  in  a  volume  of  saline  solution  equal  to 
that  of  the  serum  removed,  should  theoretically  reduce  the 
serum  protein  to  30  per  cent,  of  that  originally  present,  pro- 
vided there  were  no  renewal  of  the  plasma  protein.  But 
there  is  a  fairly  rapid  flow  of  protein  into  the  plasma  from 
supplies  existing  in  other  tissues,  so  that  the  serum  protein 
after  three  successive  bleedings  amounts  to  about  50  per  cent, 
of  the  quantity  ordinarily  present.  Notwithstanding  the 
fall  in  protein  in  the  blood-plasma,  the  quantity  of  urea  in- 
creases and  the  amino-acid  nitrogen  remains  constant. 
These  relations  are  shown  in  the  following  table  which  com- 
pares the  analysis  of  the  normal  blood  and  that  obtained  after 
five  days  of  plasmapharesis,  during  which  time  one-third  of 
the  blood  was  withdrawn  fifteen  times,  a  total  amount  of 
bleeding  equal  to  more  than  fivefold  the  quantity  of  blood  in 
the  fasting  animal. 


EFFECT    OF    PLASMAPHARESIS    UPON    THE    COMPOSITION    OF 
DOG'S   BLOOD 


' 

Total 
Protein. 

Plasma 
Protein. 

Blood- 
count. 

Urea 

N. 

Amino 

N. 

Original  blood 

Per  cent. 
19.28 

15-83 

Per  cent. 
6.38 
2.92 

Millions. 

8.50 
.6.50 

Per  cent. 

0.013 

O.021 

Per  cent. 
O.OO47 

0.0059 

After    five    days    of\ 
plasmapharesis       / '  ' 

The  reaction  of  the  organism  which  causes  an  increase  in 
the  amount  of  its  protein  metabolism  after  reducing  the 
amount  of  serum  protein  is  also  shown  in  the  experiments  of 
Taylor  and  Lewis,1  who  withdrew  blood  repeatedly  at  hourly 
intervals  and  substituted  saline  for  it  in  a  dog.  In  this  man- 
ner the  quantity  of  serum  proteins  was  reduced  to  only  2.7 
per  cent.,  although  the  quantity  of  amino-acid  nitrogen  and 
of  urea  increased  in  the  serum. 

1  Taylor  and  Lewis:  "Journal  of  Biological  Chemistry,"  1915,  xxii,  72. 


84  SCIENCE    OF    NUTRITION 

These  facts  accord  with  the  older  work  of  Bauer1  in  Voit's 
laboratory,  who  found  an  increased  nitrogen  elimination  in 
the  urine  following  bloodletting. 

Summarizing  this  discussion,  it  becomes  clear  that  though 
the  body  is  built  up  of  proteins  which  are  aggregates  of  amino- 
acids,  these  same  amino-acids  occur  free  in  only  minimal 
amounts,  4  parts  in  100,000  in  blood,  for  example,  and  40  to  80 
parts  in  100,000  in  muscle.  These  small  amounts  are  con- 
stantly present  and  apparently  are  the  precursors  of  urea. 
After  giving  meat  in  large  quantity  the  amino-acid  concentra- 
tion rises  in  the  blood,  but  not  in  the  tissues,  for  in  the  tissues 
the  amino-acids  are  either  destroyed  with  the  production  of 
urea  or  they  are  reconstructed  into  body  protein,  thus  be- 
coming "deposit  protein"  (see  p.  286).  When  starvation 
takes  place  it  is  obvious  that  the  quantity  of  protein  destroyed 
may  depend  upon  the  protein  condition  of  the  cells  them- 
selves, and  that  in  the  presence  of  much  "deposit  protein" 
this  may  be  metabolized  in  large  quantity  during  the  first  few 
days,  as  is  indicated  by  a  high  nitrogen  elimination  in  the 
urine. 

This  principle  appears  not  only  in  the  dog,  as  before 
stated,  but  also  in  man.  This  is  shown  in  the  experiments  of 
Karl  Thomas  (see  p.  275),  narrated  by  Rubner,2  although  in  this 
work  carbohydrates  were  ingested.  The  daily  diet  of  a  man 
contained  89  grams  of  protein  nitrogen  or  4.5  per  cent,  of  the 
total  protein  nitrogen  content  of  his  organism.  During  the 
last  day  of  this  diet  the  man  eliminated  77.7  grams  of  nitrogen 
in  the  urine.  Then  the  man  was  given  a  diet  of  starch  and 
sugar,  both  of  which  were  free  from  protein,  and  the  nitrogen 
elimination  in  the  urines  of  successive  days  was  determined  as 
follows:  28.3;  10.7;  5.15;  5.16;  4.72;  3.93;  3.46;  nine-day 
interval:  3.06;  2.31;  2.16.  The  gradual  elimination  of 
"deposit  protein"  with  the  tendency  of  the  total  protein 
metabolism  to  fall  to  lower  and  lower  levels  is,  therefore,  a 

1  Bauer:   "Zeitschrift  fur  Biologie,"  1872,  viii,  567. 

2  Rubner:   "Archiv  fur  Physiologie,"  1911,  p.  61. 


STARVATION  85 

concomitant  of  protein  starvation.  It  seems  that  it  is  this 
gradual  metabolism  of  "deposit  protein,"  in  addition  to  the 
constant  and  necessary  metabolism  of  the  protein  built  into 
living  substance  of  the  cells,  which  determines  the  higher  level 
of  the  protein  metabolism  during  the  early  days  of  fasting. 

During  true  fasting  it  is  quite  possible  that  the  full  ex- 
tent of  protein  metabolism  is  not  measured  by  the  nitrogen 
in  the  urine,  for  it  may  be  that  muscle  proteins  are  con- 
verted into  amino-acids  which  are  transported  to  other  or- 
gans, to  the  heart,  for  example,  for  the  replenishment  of  an 
organ  which  scarcely  loses  weight  during  the  ordeal  of  life 
without  food.  Such  a  procedure  would  be  akin  to  the 
development  of  the  genital  organs  of  the  salmon  already 
described. 

It  will  be  perceived  that  although  Voit's  term  "circulating 
protein"  is,  generally  speaking,  a  misnomer,  yet  it  served  the 
useful  purpose  of  sharply  differentiating  the  more  resistant 
behavior  of  living  tissue  protein  from  that  of  ingested  protein, 
and  from  the  material  now  known  as  "deposit  protein,"  in- 
gested protein  being  very  readily,  and  deposit  protein  quite 
readily,  metabolized. 

This  point  is  furthermore  well  illustrated  by  the  behavior 
of  gelatin.  Voit  has  demonstrated  that  although  gelatin  can 
never  be  converted  into  tissue  protein  nor  retained  in  the 
body,  its  ingestion  may  in  part  prevent  the  combustion  of  the 
living  protein  tissue  of  the  body  (see  page  156). 

The  amount  of  protein  metabolized  by  a  starving  animal 
in  good  condition  bears  a  constant  relationship  to  the  total 
metabolism  involved.  Even  in  different  animals  this  con- 
stancy is  observed.  E.  Voit1  calls  attention  to  the  fact  that 
the  nitrogen  elimination  is  not  dependent  on  the  weight  of  the 
animal,  since  a  pig  of  115  kilos  produces  0.06  gram  per  kilo, 
whereas  a  guinea-pig  weighing  but  0.6  kilo  eliminates  0.65 
gram  of  nitrogen  per  kilo,  or  ten  times  as  much.  However,  a 
comparison  of  the  percentage  of  the  total  energy  derived  from 

1  E.  Voit:   "Zeitschrift  fur  Biologie,"  1901,  xlu  188. 


86 


SCIENCE    OF   NUTRITION 


protein  in  fasting  animals  in  good  condition  (i.  e.,  with  con- 
siderable fat)  varies  within  much  narrower  limits — between 
7.3  and  16.5  per  cent.    This  is  shown  in  the  following  table: 

NITROGEN  METABOLISM   OF   DIFFERENT  ANIMALS   IN 
STARVATION. 


Animal. 


Pig 

Man 

Dog  I 

Dog  II.  . . . 
Dog  III. . . 

Rabbit 

Goose 

Fowl 

Guinea-pig 


N 

Elimination. 

Weight  in 
Kg. 

Total. 

Per  Kg. 

Per  Sq.  M. 
Surface. 

115.0 

6.8 

O.06 

3-2 

63-7 

12.6 

0.20 

6.4 

28.6 

5-i 

0.18 

5-2 

18.7 

3-8 

O.20 

4.6 

7.2 

2.2 

O.30 

5-2 

2.7 

1.2 

0.46 

4.8 

3-3 

0.8 

0.23 

3-3 

2.1 

0.7 

0.34 

4.2 

0.6 

0.4 

0.65 

4-2 

Percentage 

of  Calories 

from  Protein. 


7-3 
15-6 
13.2 
10.7 
13-5 
16.5 

7-4 
1 0.0 
10.8 


It  is  evident  from  the  above  that  an  average  of  90  per  cent, 
of  the  energy  of  the  fasting  metabolism  may  be  supplied  by 
non-protein  material.     This  material  is  fat  (see  page  27). 

If  a  fasting  organism  be  kept  at  the  same  temperature  and 
under  the  same  conditions  as  regards  the  performance  of  exter- 
nal work,  the  metabolism  is  remarkably  even  from  day  to  day. 

Hanriot  and  Richet1  showed  the  even  absorption  of  oxygen 
and  elimination  of  carbon  dioxid  during  the  early  days  of 
fasting  in  man,  as  is  illustrated  in  this  table: 

Liters  Oj  Liters  CO2 

per  Hour.  per  Hour. 

After  17  hours'  fast i7-4  J5-3 

"     24      "         "   16.85  14.15 

"      2g       "         "    16.05  14.3 

"     46      "         "   16.9  14-35 


Later  Lehmann  and  Zuntz2  made  some  experiments  on  the 
professional  faster  Cetti.  They  analyzed  his  urine  and  feces, 
and  also  obtained  two  samples  of  the  carbon  dioxid  eliminated 

1  Hanriot  and  Richet:  "  Comptes  rendus  de  l'Academie  des  Sciences,"  1888, 
cvi,  496. 

2 Lehmann  and  Zuntz:   "Arch  f.  pathol.  Anat.,"  1893,  cxxxi,  Suppl.,  23. 


STARVATION 


87 


between  10  and  11  a.  m.,  each  period  of  collection  lasting  from 
ten  to  fourteen  minutes.  In  other  words,  the  carbon  dioxid 
output  was  determined  for  only  twenty  to  twenty-six  minutes 
daily.  From  these  data  the  total  day's  metabolism  was 
calculated.  This  apparatus  as  used  by  Zuntz  has  the  ad- 
vantage that  it  can  be  made  in  portable  form,  and  may  be 
carried  on  the  back  in  mountaineering.  The  person  inspires 
through  a  mouth-piece  provided  with  a  plate  of  hard  rubber 
which  fits  between  the  lips  and  the  teeth.  The  nostrils  are 
closed  with  a  clamp.  The  inspired  air  is  drawn  through  a 
valve  and  the  expired  air  is  forced  through  another  valve  to 
a  gas-meter.  Arrangements  are  also  provided  for  the  gas 
analysis  of  portions  of  the  expired  air.  Trustworthy  results 
are  obtained  only  when  the  person  under  investigation  is 
accustomed  to  the  apparatus.  It  is  of  especial  value  when 
pronounced  temporary  variations  in  the  metabolism  are  to  be 
measured. 

The  record  of  the  metabolism  of  Cetti  during  a  ten  days' 
fast  was  as  follows: 


METABOLISM   OF 

CETTI   IX  STARVATION 

Fasting  Days. 

Protein. 

Fat. 

Calories 

from 
Protein. 

Calories 
from  Fat. 

Calories,      Calories 
Total.      '  per  Kilo. 

1  to    4 

5  to    6 

7  to    8 

9  to  10 

85.88 
69.58 
66.30 
67.96 

136.72 
I3I-30 
149-35 
132.38 

329.8 
267.3 

254.7 
261. 1 

1288.2 
1237-4 
1407-3 
1247.4 

1618 

I504 
1662 
1508 

29.00 
28.38 

31-74 
29.26 

A  very  careful  experiment  on  the  metabolism  of  a  fasting 
medical  student  twenty-six  years  old  was  made  by  Johansson, 
Landergren,  Sonden,  and  Tigerstedt.1  The  man  fasted  five 
days,  doing  light  work  in  the  respiration  apparatus.  The 
metabolism  during  these  days  was  determined.  The  excreta 
in  grams  were  as  follows: 


1  Landergren,  Sonden,  and  Tigerstedt: 
1897,  vii,  54. 


'Skandin.  Archiv  fur  Physiologie," 


88  SCIENCE    OF   NUTRITION 

METABOLISM   OF  J.   A.   IN   STARVATION 


Day  of 

N 

Elimination. 

C  Elimination. 

Fasting. 

Urine. 

Feces. 

Total. 

Urine. 

Feces. 

Respiration. 

Total. 

I 

12.04 
12.72 
13.48 
I3-56 

n-34 

0.13 
0.13 

O.I3 
O.13 
O.13 

12.17 
12.84 
13.61 
13.69 

11.47 

8.0 

8-3 

9.9 

10.3 

9-3 

I.I 
I.I 
I.I 
I.I 
I.I 

188.5 
179.4 
172.2 
169.4 
165.8 

197.6 
1888 

2 

3 

183.2 
180.8 
176.2 

4 

5 

The  evenness  of  the  carbon  and  nitrogen  elimination  is 
remarkable.  From  the  above  figures  the  following  table  of 
the  general  metabolism  is  made: 


Day  of  Fasting. 

Protein. 

Fat. 

Calories 

from 
Protein. 

Calories 
from 
Fat. 

Calories, 
Total. 

I 

2 

3 

76.1 
80.3 
85.I 
85.6 
71.7 

206.1 
191. 6 
181. 2 
177.6 
181. 2 

303-5 
320.5 

339-4 
341-4 
286.1 

1916.9 
1781.9 
1684.7 
1651-9 
1684.7 

2220.4 
2102.4 
2024.1 
1992.3 
1970.8 

4 

5 

Further  calculation  shows  the  following  relations  between 
the  weight  of  the  individual  and  the  calorific  production: 

Day  of  Weight  Calories 

Fasting.  -  in  Kilos.  per  Kilo. 

1 66.99  33-15 

2 65.71  32.00 

3 64.88  31.20 

4 63.99  31.13 

5 63.13  31.23 


On  the  fifth  day  of  fasting  it  is  seen  that  the  individual 
oxidized  71.7  grams  of  protein,  18 1.2  grams  of  fat,  and  pro- 
duced 1971  calories,  or  31.23  calories  per  kilogram  of  body 
substance.  This  is  presumably  the  minimum  compatible 
with  ordinary  life. 

Reference  has  already  been  made  to  the  notable  work  of 
Benedict  (p.  72),  "The  Influence  of  Inanition  on  "Metabolism." 


STARVATION 


89 


Here  in  seventeen  experiments  on  seven  men  the  metabolism 
was  determined  during  a  fast  of  two  days,  and  in  one  instance 
the  starvation  period  extended  over  seven  days.  In  these 
experiments  the  metabolism  of  glycogen  was  for  the  first  time 
determined.  Benedict's  fasting  individuals  were  placed  in  a 
respiration  calorimeter,  and  in  addition  to  the  usual  routine  the 
amount  of  oxygen  consumed  by  them  was  measured.  Know- 
ing the  last  factor,  Benedict  was  able  to  calculate  the  amount  of 
glycogen  destroyed  by  deducting  from  the  total  oxygen  intake 
the  part  necessary  to  oxidize  the  protein  catabolized,  and  then, 
in  the  light  of  the  knowledge  of  the  respiratory  quotient,  ap- 
portioning the  remainder  of  the  oxygen  to  the  non-protein 
carbon  dioxid  eliminated  in  such  a  way  as  to  indicate  the 
amounts  of  glycogen  and  fat  destroyed  (see  p.  60).  The 
heat  value  of  the  metabolism  thus  calculated  agreed  within 
^  of  1  per  cent,  with  the  heat  as  actually  measured  by  the 
calorimeter  in  which  the  man  lived,  whereas  if  the  non- 
protein carbon  of  the  first  day  had  been  reckoned  as  fat 
metabolized,  as  had  heretofore  been  the  custom,  the  discrep- 
ancy would  have  been  as  high  as  5  per  cent,  in  some  in- 
stances. This  shows  the  usefulness  of  a  comparison  of  direct 
and  indirect  calorimetry  (see  p.  57). 

The  results  of  Benedict's  experiment  on  an  individual  who 
fasted  for  seven  days  are  here  reproduced : 


METABOLISM   OF   S.   A.   B.   DURING   A  SEVEN-DAY  FAST. 


Grams. 

Calories. 

R.Q. 

Urine. 

Day 

Pro- 
tein. 

Fat. 

Glyco- 
gen. 

Calcu- 
lated 
from 

Metab. 

Direct- 
ly De- 
ter- 
mined. 

Per 
Kg. 

Per 

Sq. 

M. 

Ratio 

N:S. 

Ratio 
N:PsOs. 

I... 

2.. . 
3--- 
4... 
5--- 
6... 
7... 

73-4 
74-7 
78.1 
69.8 
65.2 
64.4 
.     60.8 

126.4 
147-5 
i53-o 
144-7 
144.7 
129.8 
-32-5 

64.9 
23.1 

5-4 
25.2 

8.2 
21.7 
18.7 

1796 
1790 
1785 
1734 
1636 
1547 
1546 

1765 
1768 
1797 
1775 
1649 

1553 
1568 

29.7 
29.9 
30.8 
30.8 
29.0 

27-5 
28.0 

941 
946 
969 
966 

9°5 
856 
869 

.78 
•75 
•74 
•75 
•74 
•75 
•74 

19.6 

18.6 

17-38 

16. 11 

16.26 

16.27 

16.28 

8-55 
5-55 
6-34 
4-83 
5-23 
5-19 
4.87 

9° 


SCIENCE   OF    NUTRITION 


This  complete  and  recent  experiment  reaffirms  the  princi- 
ples which  have  already  been  enunciated.  Benedict  found 
that  the  pulse-rate  showed  a  distinct  tendency  to  fall.  In  the 
above  individual  the  average  pulse-rate  was  57  on  the  first 
fasting  day  and  5 1  on  the  seventh  day. 

E.  Voit1  gives  the  following  summary  of  the  energy  re- 
quirements during  the  early  days  of  starvation  in  man : 
GENERAL  TABLE   OF   STARVATION  METABOLISM   IN  MAN 


Day 

Weight. 

Energy  in  Calories. 

Author. 

of  Fast. 

Total. 

Per  Kg. 

Per  Sq.  M. 
Surface. 

I 

I 

1  to  5 

1 

1  to  2 

70.6 

70.4 
64.9 

59-5 
56.0 

2359 
2222 
2071 
1893 
1773 

33-4 
31.6 

31-9 
•   3i-8 

3i-7 

III2 
1060 
1042 
IOI2 
985 

Pettenkofer  and  Voit. 

Pettenkofer  and  Voit. 

Tigerstedt. 

Zuntz  and  Lehmann. 

Zuntz  and  Lehmann. 

To  this  may  be  added  the  average  results  of  the  many 

experiments  by  Benedict: 

METABOLISM  IN  THE   EARLY  DAYS   OF   STARVATION 

ist  Day.     2D  Day.        3D  Day.    4TH  Day.      sth  Day. 

No.  of  experiments 18  17  9  5  2 

Average  calories  per  kg 30.7  31.8  31.0  29.6  28,5 

Average  calories  per  square!  Q  Q  QQ„ 

meter  surface  (Meeh)        )~*>2         I028  "x  938  88s 

This  minimal  metabolism  requirement  of  the  fasting  organ- 
ism appears  remarkably  constant  in  different  men.  Not  only 
is  the  total  metabolism  the  same,  but  also  the  amounts  of 
protein  and  fat  which  yield  the  energy  are  the  same.  This 
is  shown  by  comparing  the  nitrogen  excretion  of  the  different 
f asters  during  the  first  days  of  fasting.     These  are  as  follows: 

Cetti.2  Breithaupt.3  Succt.4  J.  A.5  Succi.* 

1 13-55  IO-QI  I3-8i  12.17  17.00 

2 12.59  9-92  11.03  12-85  11.20 

3 13-12  13.29  13.86  13.61  10.55 

4 12.39  12.78  12.80  13-69  10.80 

5 10.70  10.95  12.84  n-47  n. 19 

6 10.10  9.88  10.12  11.01 

1  Voit,  E.:   "Zeitschrift  fiir  Biologie,"  1901,  xli,  114. 
2Munk:   "Arch.  f.  Path.  Anat.,"  1893,  cxxxi,  Suppl.  25. 
3  Munk:   Ibid.,  p.  68.  4Luciani:   "Das  Hungern,"  1890. 

5  Johansson,  Landergren,  Sond6n,  and  Tigerstedt:  "Skandin.  Archiv.  fiir 
Physiol.,"  1897,  vii,  54. 

8  Freund,  E.  and  O.:  "Wiener  klinische  Rundschau,"  1901,  xv,  91. 


STARVATION 


91 


It  is  thus  evident  that  if  the  organism  has  previously  been  well 
nourished,  the  fasting  metabolism  is  remarkably  even,  about 
13  per  cent,  of  the  total  energy  being  derived  from  protein  and 
87  per  cent,  from  fat. 

During  prolonged  fasting  the  nitrogen  output  sinks  much 
below  the  figures  of  the  earlier  days.  Thus  a  woman  twenty- 
four  years  old  averaged  4.15  gm.  from  the  thirteenth  to  the 
twenty-fifth  day  of  fasting.1  A  girl  nineteen  years  old  whose 
esophagus  had  been  occluded  by  drinking  sulphuric  acid  ex- 
creted 2.8  grams  of  nitrogen  on  the  sixteenth  day  of  fasting.2 
An  invalid  of  Tuczec's3  averaged  4.25  grams  of  nitrogen 
between  the  fifteenth  and  twenty-first  days.  Under  Luciani's 
observation  Succi  excreted  4.08  grams  on  the  twenty-ninth 
day,  and  under  E.  and  O.  Freund  his  nitrogen  excretion  was 
2.82  grams  on  the  twenty-first  day.  The  latter  authors  say 
that  after  this  there  was  a  sudden  rise  in  the  amount  of  nitrogen 
and  chlorin  in  the  urine,  suggesting  the  so-called  premortal 
rise,  which  caused  them  to  stop  the  experiment.  About  3 
grams  of  nitrogen  in  the  urine  or  a  daily  destruction  of  18.75 
grams  of  protein  would  seem  to  be  the  lowest  extreme  of 
protein  metabolism  in  the  emaciated  organism  after  a  pro- 
longed fast.  The  analyses  by  E.  and  0.  Freund  of  Succi's 
urine  during  a  fast  of  twenty-one  days  was  the  first  complete 
record  of  the  sort.  The  daily  nitrogen  excretion  is  given  in 
grams  below: 

DAILY   NITROGEN   EXCRETION  OF   SUCCI   IN   STARVATION 


1  Seegen:   "Wiener  Acad.  Sitz.  Ber.,"  Bd.  xxxiii,  2  Abth. 
2Schultzen:   "Archiv  fur  Anatomie  und  Physiologie,"  1863, 
3Tuczec:   "Arch,  fur  Psychiatrie,"  1884,  xv,  784. 


P-3i- 


92 


SCIENCE    OF   NUTRITION 


The  nitrogen  and  total  sulphur  ran  together  in  the  urine 
in  the  proportion  of  17.3  N  :  1  S.  Munk  found  the  ratio 
^  to  be  14.7  in  Breithaupt  and  15.1  in  Cetti,  and  Benedict 
(see  p.  89)  found  16.27  during  the  fifth,  sixth,  and  seventh  days 
of  starvation.  A  similar  relation  between  N  and  S  is  found 
in  muscle.  The  sulphur  is  believed  to  be  derived  exclusively 
from  the  breaking  down  of  protein. 

The  nitrogen  and  total  phosphoric  acid  (P2O5)  in  the  urine 
are  not  found  in  the  same  ratio  as  that  in  which  they  exist 
in  meat  (7.6  :  1),  but  there  is  a  greater  phosphoric  acid  excre- 
tion. This  is  also  true  of  the  calcium  excretion.  This 
greater  excretion  is  due  to  the  metabolism  of  the  bones 
(Munk).  E.  and  O.  Freund  found  that  the  ^  fell  from  5.7 
on  the  first  day  of  Succi's  starvation  to  between  4.2  and  4.4 
during  the  subsequent  periods.  Munk  found  this  value  to  be 
4.4  in  Cetti  during  ten  days  and  5.1  in  Breithaupt  during  six 
days  (consult  table  on  p.  96). 

Albumin  is  of  frequent  occurrence  in  the  starvation  urine 
of  man  and  animals. 


URINARY  ANALYSIS  OF  VICTOR  BEAUTE  ON  THE  FIRST,  THIRD, 
TWELFTH,  AND  FOURTEENTH  DAYS  OF  FASTING. 

WEIGHT  IN   GRAMS. 


Total  N 

UreaN. 

Ammonia  N. 
Uric  arid  N. . 
Purin  base  N 
Creatinin  N. 
Creatin  N. . . 

TotalS 

Total  P0O5. . 

CI 

Ca 

Mg 

K 

Na 


Day  of 

Fasting. 

1ST. 

3D- 

I2TH. 

IO.5I 
8.96 

13-72 
12.26 

8.77 
6.62 

O.4O 
O.I2 

o-73 
0.06 

1.05 
0.17 

0.029 

0.032 

0.023 

O.42 

0.34 

O.30 

0.02 

O.614 

2.26 

0.09 

0.801 

2.98 

0.09 

o-577 

i-5S 

3-2 

i-5 
0.216 

0.131 
0.865 

0.18 

7.78 

5-99 
o-73 
0.17 

0.24 
0.10 
o-536 

1-25 

0.24 
0.096 

0.037 
0.515 

0.096 


STARVATION 


93 


A  modern  chronicle  of  the  urinary  excretion  during  fasting 
is  presented  in  an  experiment  by  Cathcart1  on  a  professional 
faster,  thirty-one  years  old,  a  part  of  which  is  reproduced  on 
p.  92. 

In  this  experiment  the  ammonia  excretion  rose  to  meet  an 
accompanying  acidosis.  The  creatinin  excretion  gradually  fell, 
whereas  the  creatin  excretion  (see  p.  211)  remained  quite  con- 
stant. The  ratio  between  the  nitrogen  and  sulphur  elim- 
ination averaged  15  N  :  1  S,  or  similar  to  the  relation  found 
in  muscle,  which  is  14  N  :  1  S.  The  relatively  large  potassium 
excretion  and  the  small  sodium  excretion  indicated  respectively 
the  destruction  of  body  tissues  which  are  all  rich  in  potassium 
salts  and  the  conservation  of  the  body's  sodium  chlorid 
supply. 

A  communication  by  Brugsch2  shows  that  the  quantities 
of  /3-oxybutyric  acid  and  acetone  in  the  urine  become  very 
great  in  extreme  hunger.  The  experiment  was  also  on  Succi, 
between  the  twenty-third  and  the  thirtieth  days  of  starvation, 
and  showed  the  following  remarkable  values: 

ACETONURIA  IN  STARVATION    (SUCCI) 


Starvation  Day. 


23d. 
24th 
25th 
26th 
27th 
28th 
29th 
30th 


N  jn  Grams. 


5-87 
6.41 
6.27 
6.18 
6.30 

4-43 
4.19 
8.42 


18-oxYBUTYRic 
Acid  in  Grams. 


9.24 
8.43 
9-85 
5-28 

11.62 
6.99 
9. 15 

13.60 


Acetone  in 
Grams. 


0.569 
0.410 
0.463 
0.569 
O.525 
0-339 
0.242 
0.115 


The  excretion  of  urea  nitrogen  ran  between  54  and  70  per 
cent.,  and  the  ammonia  nitrogen  between  15.4  and  35.3  per 
cent,  of  the  total  nitrogen  in  the  urine.  The  high  ammonia 
neutralized  the  very  considerable  acidosis. 

1  Cathcart:   " Biochemische  Zeitschrift,"  1907,  vi,  109.  _ 

2  Brugsch:    "Zeitschrift  fur  ex.  Pathologie  und  Therapie,"  1905,  i,  419. 


94 


SCIENCE    OF   NUTRITION 


Grafe1  reports  the  excretion  of  16.25  and  15.41  grams  of 
urinary  acetone  bodies  during  the  sixteenth  and  eighteenth 
days  of  fasting  in  a  stuporous  patient  suffering  from  katatonic 
rigidity  and  lying  in  deep  sleep  on  these  days. 

Folin  and  Denis2  have  described  results  concerning  the 
development  of  acidosis  in  two  obese  women,  patients  of  Dr. 
J.  H.  Means.3  Mrs.  M.,  weighing  108  kilograms,  whose  height 
was  149.7  cm-  (4  ft.  1  in.),  underwent  3  different  periods  of 
fasting,  with  the  following  results: 

ACIDOSIS   IN   OBESITY 


No.  of  Fast. 

Day  of 
Fast. 

Urine 
N. 

0-OXY- 
BUTYRIC 

Acid. 

NH3. 

Acidity 

N/io 
Alkali. 

I 

II 

4 
5 
4 

Grams. 
0.4 
5-2 
4-5 

Grams. 

18.47 
13-54 
17-34 

Grams. 
2.50 
I.50 
0.81 

Cc. 

695 

655 

Ill 

300 

Headache  and  nausea  were  present  on  these  fourth  and 
fifth  days  of  fasting,  symptoms  which  disappeared  as  if  by 
magic  after  the  patient  took  one  piece  of  toast  and  a  cup  of  tea. 
The  authors  state,  "If  the  preceding  subject  was  fat,  our  next 
one,  Mrs.  B.,  was  a  veritable  pork  barrel."  Mrs.  B.  weighed 
178  kilograms  and  measured  163.5  cm-  (5  ft-j  4^  in-)  in  height. 
She  did  not  show  the  same  intensity  of  acidosis  manifested 
by  the  other  patient,  the  largest  quantity  of  /3-oxybutyric  acid 
eliminated  reaching  only  7.2  grams  on  the  seventh  day  of  a 
third  fasting  period.  From  these  results  it  was  concluded 
that  obesity  itself  was  not  a  predisposing  cause  of  acidosis. 
In  general,  it  was  observed  that  the  protein  metabolism  was 
low  in  these  persons  in  whom  ample  fat  was  present  (see  p.  100), 
that  repeating  the  fast  lowered  the  protein  metabolism  (see 
Hawk,  p.  104),  and  also  that  repeated  fastings  habituated  the 
organism  to  the  complete  oxidation  of  fats  as  evidenced  by  a 
decrease  in  the  amount  of  /3-oxybutyric  acid  eliminated  on 

1  Grafe:    "Zeitschrift  fiir  physiologische  Chemie,"  1910,  lxv,  21. 

2  Folin  and  Denis:   "Journal  of  Biological  Chemistry,"  1915,  xxi,  183. 

3  Means:   "Journal  of  Medical  Research,"  1915,  xxxii,  121. 


STARVATION  95 

corresponding  days  of  the  several  fasts.  In  this  connection 
the  observation  of  Abderhalden  and  Lampe,1  that  fasting 
progressively  increases  the  power  of  dog's  blood  to  split 
tributyrin,  is  of  significance  in  showing  adaptative  power  by 
the  organism.  Folin  and  Denis  conclude  that  the  method 
of  repeated  fasting  applied  to  the  obese  is  safe,  harmless,  and 
effective,  provided  the  intensity  of  the  acidosis  be  carefully 
followed. 

In  a  way  the  results  here  mentioned  are  all  summarized  in 
the  extended  work  of  Benedict2  upon  a  subject  L.,  who  fasted 
for  thirty-one  days.  Benedict  found  no  evidence  of  any  dis- 
turbance of  the  higher  mental  functions  of  the  subject.  He 
found  a  lowered  power  of  endurance  during  the  fast,  but,  ac- 
cording to  tests  made  a  year  later,  could  discover  no  lasting 
evil  effect  of  the  fast  either  upon  muscular  strength  or  mental 
activity.  It  is  recorded  that  no  feces  were  passed  during  the 
entire  fast. 

The  chart  (page  96)  illustrates  the  principal  data  and  a  table 
(page  97)  is  also  given  which  shows  the  most  important  deter- 
minations made  on  the  first,  eleventh,  twenty-first,  and  thirty- 
first  days  of  fasting. 

The  lowest  average  heat  production  of  the  fasting  subject 
when  in  the  bed  calorimeter  during  the  night  was  on  the  thir- 
tieth day,  and  amounted  to  1025  calories  calculated  for  a 
twenty-four-hour  period,  or  661  calories  per  square  meter  of 
surface  (Du  Bois  Height- weight  Formula). 

During  the  fast  the  man  lost  277  grams  of  nitrogen  from 
his  body.  If  one  may  estimate  with  Rubner  that  a  man  under 
conditions  of  normal  nutrition  contains  30  grams  of  nitrogen 
per  kilogram  of  body  weight,  then  the  original  nitrogen 
content  of  the  subject  was  1788  grams.  A  loss  of  277  grams 
would  represent  16  per  cent.  This  loss  occurred  during  a 
period  when   the  heat  production   fell  from    1441    to   1025 

1  Abderhalden  and  Lampe:  "Zeitschrift  fur  physiologische  Chemie,"  1912, 
lxxviii,  398. 

2  Benedict,  F.  G.:  "A  Study  of  Prolonged  Fasting,"  Carnegie  Institution 
of  Washington,  1915,  Publication  203. 


OXYGEN  AND  CARBON 
OIOXIDE.  cc 


ALVEOLAR  C0S  TENSION,  mm 


BLOOD  PRESSURE. 


HEATPER24HRS.CALS.- 


BODY  TEMPERATURE,  *C 


MEATPERKHAPOHMLCALJ. 


RESPIRATORY  QUOTIENT 


RESPIRATION  RATE 
PULSE  RATE 


CHLORINE  (CI).  GMS.' 


TOTAL  NITROGEN.  GMS. 


PHOSPHORUS  (PjOj).  CMS. 

CARBON  IN  URINE.  GMS.  I 
B-OXYBUTYRIC  ACID.  CMS.) 


URICACIO-N,GM. 
TOTAL  SULPHUR  (Si  CM. 

AMMONIA-N,  CMS.- 


[NUTRITION  LABORATORY  OF  THE  CARNEGIE  INSTITUTION  OF  WASHINGTON.  BOSTON.  MASSACHUSETTS] 

METABOLISM  CHART  OF  A  MAN  FASTING  31  DAYS 

APRIL  14 -MAY  15.  1912 
I  2  3  4  5  6  7  B  9  10  1 1  12  13  14  15  16  17  16  19  20  21  22  23  24  25  26  27  28  29  30  31 


1/2  3  4  5  6  7  6  9  10  1 1  12  13  14  15  16  1.7  18  19  20  21  22  23  24  25  26  27  28  29  30  3* 


96 


Fig.  4- 


STARVATION 


97 


SUBJECT  L.     HEIGHT,  170.7  CM.     ONLY  DISTILLED  WATER  WAS 
TAKEN   DURING  THIS   FAST 


Day  of  Fasting. 


Body  weight,  kg 

Rectal  temperature  at  7  A.  M 

Pulse-rate,  morning,  awake 

Hemoglobin  in  per  cent 

Alveolar  CO2  tension  (Haldane) ... 
Urine:    Total  solids 

Total  N 

Urea  N 

Ammonia  N 

Uric  acid  N 

Creatinin  +  Creatin  N 

Chlorin 

P206 

N  :  P205 

S 

N:S... 

/3-oxybutyric  acid 

Ca 

Mg 

K 

Na 

C  :  N. 

Calories  N 

Loss  of  flesh  calculated  from  N  loss 

C02,  night,  c.c.  per  minute 

O2,  night,  c.c.  per  minute 

R.  Q.,  night 

H20  per  hour 

Per  cent,  of  calories  from  protein .  . 
Calories,  indirect,  twenty-four  hours' 

complete  rest 

Calories  per  square  meter  (DuBois), 

twenty-four  hours 

Calories  per  kilogram,   twenty- four 
hours 


59.60 


74 
90 
32.8 

43-51 
7.10 
5-68 
0.41 
0.1 1 2 
0.48 

3-77 
1.66 
4.28 
0.46 
15-4 


0.217 
0.046 
1.630 
2.070 
0.820 

9-i5 
213 

165 
212 
0.78 

22.8 

10.6 

1441 

843 

24.2 


nth 

2ISt 

53-88 

50-49 

36.54 

36.O4 

61 

59 

85 

88 

28.7 

42.05 

31.88 

10.25 

7-93 

7.66 

5-54 

1.58 

i-57 

0.116 

0.112 

0.49 

0.38 

0.36 

0.18 

i-95 

1.60 

5.26 

4.96 

0.62 

0.51 

16.5 

15-5 

1.4 

5-o 

0.220 

0.237 

0.072 

0.053 

1.006 

0.644 

O.IOO 

0.066 

0.936 

1.083 

10.73 

11.98 

308 

238 

128 

112 

176 

154 

0.72 

o.73 

18.3 

14.6 

19.6 

16.5 

1 193 

1032 

73  2 

653 

22.1 

20.4 

31st 


47-39 

35-96 

60 

92 

31.8* 

27.07 
6-94 
4.84 
1.24 
0.122 
0.32 
0.13 
1.32 
5.26 
0.49 

14.2 

4-5 

0.138 

0.052 

0.606 

0053 

1.062 

"•53 
208 

115 
160 
0.72 

17.9 

14.4 

I072f 

701 1 

22.6 


Previous  day  =  27.8.     f  Previous  day  =  1025.     J  Previous  day  =  661 


calories,  a  reduction  of  29  per  cent.  It  is,  therefore,  evident 
that  the  fall  in  metabolism  reaches  greater  proportions  than 
does  the  fall  in  the  mass  of  protoplasmic  tissue. 

There  seems  to  be  a  specific  reduction  in  metabolism 
coincident  with  undernutrition  (see  p.  476).  Unfortunately, 
when  food  was  taken  after  the  fast  digestive  disturbances 


98 


SCIENCE   OF   NUTRITION 


marred  the  records  of  this  subject.  It  would  have  been 
interesting  to  ascertain  whether  his  metabolism  on  the 
second  or  third  day  of  food  ingestion  was  normal  according 
to  the  unit  of  surface. 

Benedict  calls  attention  to  the  fact  that  there  is  a  paral- 
lelism between  the  amounts  of  magnesium  and  of  nitrogen 
eliminated  in  the  urine. 

The  following  analysis  of  the  derivation  of  the  source  of 
the  mineral  constituents  in  the  urine  of  Benedict's  subject  L. 
may  be  made.  Katz1  reports  upon  the  quantities  of  the  min- 
eral constituents  of  human  flesh,  as  obtained  from  a  suicide 
on  the  day  of  death: 

MINERAL  ANALYSIS   OF   FRESH   HUMAN  MUSCLE 


Parts  in  1000 

K. 

Na. 

Fe. 

Ca.                Mg. 

P205. 

CI. 

s. 

3.20 

O.80 

0-15 

O.075          O.212 

4.68 

0.70 

2.08 

On  this  basis  a  calculation  has  been  made  of  the  mineral 
content  of  the  "flesh"  computed  to  have  been  destroyed  on 
three  different  days  in  the  fasting  subject  L.,  and  these 
calculated  values  have  been  compared  with  the  minerals 
actually  excreted  in  the  urines  of  these  days.  The  following 
table  presents  these  details : 


SUBJECT  L.  ESTIMATED  SALT  SUPPLY  FROM  "FLESH"  METAB- 
OLIZED ON  THE  ASSUMPTION  THAT  THIS  WAS  MUSCLE 
TISSUE,  COMPARED  WITH  THE  LOSS  OF  SALTS  IN  THE  URINE 


In  308  g.  flesh 

In  urine 

Difference.  . .  . 

In  238  g.  flesh. 

In  urine 

Difference .... 

In  208  g.  flesh 

In  urine 

Difference .... 


Day 

OF 

Fast. 

K. 

n 

0.986 
1.006 

—0.020 

22 

0.762 

0.643 

+0.119 

31 

0.665 

0.606 

+0.059 

Na. 

Ca. 

Mg. 

P206. 

CI. 

0.246 

0.023 

0.065 

1.44 

0.22 

O.IOO 

0.220 

0.072 

1-95 

0.36 

+0.146 

-0.197 

—0.007 

-O.51 

—0.14 

0.190 

0.018 

0.050 

1. 11 

0.17 

0.066 

0.237 

0.053 

1.60 

0.18 

+0.124 

—0.219 

—0.003 

-0.49 

— O.OI 

0.166 

o.ci6 

0.044 

0.97 

0.15 

0.053 

0.138 

0.052 

1-32 

0.13 

+0.113 

—0.122 

—0.008 

-0.35 

+0.02 

0.64 
0.62 

+  0.02 

0.50 
0.51 

—  O.OI 

0.43 
0.49 

—0.06 


Katz:   "Pfliiger's  Archiv,"  1896,  lxiii,  1. 


STARVATION 


99 


It  is  apparent  that  the  quantities  of  potassium,  magnesium, 
and  sulphur  eliminated  in  the  urine  are  essentially  those  which 
might  have  been  derived  from  the  tissue  destroyed.  Sodium 
is  constantly  retained  by  the  organism,  whereas  the  loss  of 
calcium  and  P205  represents  osseous  destruction.  Since  bones 
contain  24.48  per  cent,  of  calcium  and  only  0.1  per  cent,  of 
magnesium,  the  loss  of  magnesium  from  this  source  would  not 
be  appreciable. 

It  seems  clearly  evident  that  the  urinary  waste  of  mineral 
constituents  is  largely  composed  of  metabolized  muscle  or 
tissue  analogous  in  composition  to  muscle,  and  of  metabolized 
bone  tissue. 

It  has  already  been  set  forth  that  the  general  metabolism  is 
extremely  even  in  fasting,  and  it  may  be  added  that  existing 
evidence  shows  that  the  intermediary  metabolism  has  a  similar 
character.  Thus  Stiles  and  Lusk1  found  in  a  fasting  dog  made 
diabetic  with  phlorhizin  that  whereas  the  quantity  of  nitrogen 
and  sugar  eliminated  slowly  fell,  the  ratio  between  the  two 
(the  Dextrose  :  Nitrogen  or  D  :  N  ratio)  remained  constant. 
This  is  shown  in  the  following  table: 


CONSTANT  RATIO  BETWEEN  DEXTROSE  PRODUCTION  AND  N 
ELIMINATION  IN   STARVATION 


Period. 

D  per  Hour. 

N  per  Hour. 

D  :N. 

15  hours 

6       "    

2.61 

2-39 
2.51 

2.36 
2.32 

°-735 
0.720 
0.683 
0.666 
0.687 
0.670 
0.643 
0.642 

3-56 

3       "    

12       "    

3.60 
3-65 

3       "    

6       "    

3       "    

3.66 
3.62 

11       "    

The  hour-to-hour  sugar  production  from  protein  is  there- 
fore even  and  constantly  proportional  to  the  protein  metab- 
olism. 


Stiles  and  Lusk:   "American  Journal  of  Physiology,"  1903,  x,  77. 


IOO  SCIENCE    OF   NUTRITION 

The  length  of  life  under  the  condition  of  starvation  gen- 
erally depends  upon  the  quantity  of  fat  present  in  the  organism 
at  the  start.  The  quantity  of  fat  and  protein  in  an  animal 
at  the  beginning  of  starvation  or  at  any  time  during  starva- 
tion may  be  estimated  if  the  day-to-day  metabolism  be  deter- 
mined and  if  the  whole  animal  be  analyzed  for  fat  and  protein 
at  the  time  of  death.  The  sum  of  the  quantities  remaining  in 
the  body,  and  the  quantity  of  waste  of  previous  days,  will 
give  the  composition  of  the  animal  at  any  definite  date 
during  the  experiment.  E.  Voit1  shows  that  a  rabbit  with  an 
original  fat  content  of  7  per  cent,  lived  nineteen  days  and  lost 
49  per  cent,  of  his  body  protein.  Another  rabbit  with  an  orig- 
inal fat  content  of  only  2.3  per  cent,  lived  but  nine  days,  while 
the  loss  of  body  protein  amounted  to  35  per  cent.  At  the 
death  of  these  rabbits  the  amount  of  fat  found  was  very  small, 
and  the  general  vitality  toward  the  end  was  almost  exclusively 
maintained  by  the  combustion  of  protein.  Other  animals, 
however,  which  lost  22  to  26  per  cent,  of  their  protein  con- 
tained considerable  fat  at  the  time  of  death  (see  table,  p.  103). 
E.  Voit  finds  that  the  greater  the  amount  of  fat  in  the  body, 
the  less  is  the  protein  metabolism.  In  animals  of  equal  fat 
content  the  relation  between  the  amount  of  fat  and  the  amount 
of  protein  oxidized  in  the  cells  in  starvation  is  always  the  same. 
When  there  is  no  fat,  protein  may  burn  exclusively.  From 
this  it  follows  that  the  quantity  of  the  protein  metabolism  in 
starvation  depends  upon  the  amount  of  fat  in  the  body. 

E.  Voit2  has  prepared  the  following  table  from  an  experi- 
ment of  SchondorfP  upon  a  fasting  dog.  The  quotient 
Fat  ^nSt  giyes  tne  rati°  between  these  two  components  of 
the  organism  at  the  time  specified.  The  ratio  ^ne^/totai" 
gives  the  percentage  of  the  total  energy  derived  from  the  pro- 
tein metabolism.  The  dog  died  on  the  thirty-eighth  day  of  his 
fast: 

1  E.  Voit:   "Zeitschrift  fur  Biologie,"  1001,  xli,  545. 

2E.  Voit:   Ibid.,  p.  520. 

3  Schondorff:   "Pfliiger's  Archiv,"  1897,  lxvii,  430. 


STARVATION 


IOI 


PROTEIN  METABOLISM   IN   STARVATION  AS   INFLUENCED   BY 
THE   FAT   CONTENT  OF  THE  ANIMAL 


Starvation 
Day. 

Weight 
in  Kg. 

N  Content 
Fat  Content. 

Excreta 

N 
in  Grams. 

Energy  per 
Sq.  Meter 
Surface. 

Energy  Protein 
Energy  Total. 
Reduced  to  %. 

4th  to  13th... 
14th  to  15th.. 
16th  to  23d.  . 
24th  to  30th.. 
31st  to  35th.. 

36th 

37th 

38th 

22.4 
20.7 
19.7 
18.7 
17.4 
16.2 
15-7 
15-5 
15.2 

0.25 
0.29 

0.34 
O.40 

0.57 
0.87 
1. 19 
i-34 
i-5i 

7.91 
5-38 
5-7° 
5-7i 
5-92 
6.62 
7.41 
8.41 
8.89 

1040 
974 
959 
944 
919 
901 
889 
887 
881 

26.5 
16.2 
18.1 
19.1 
21.3 
25.6 
29-5 
33-8 
36.6 

E.  Voit  finds  that  the  amount  of  protein  metabolism 
depends  so  absolutely  upon  the  relation  between  the  amount 
of  fat  and  protein  in  the  body  (the  ^t^St)  tnat>  knowing  this 
ratio,  he  says  he  can  estimate  the  relative  protein  metabolism. 
When  the  ratio  rises  to  4.84  in  the  rabbit,  then  98.3  per  cent,  of 
the  total  energy  may  be  derived  from  protein.  Had  fat  still 
been  present  in  considerable  quantity  the  protein  metabolism 
would  have  remained  low.  This  is  the  law  which  governs  the 
gradual  rise  in  the  protein  metabolism  during  starvation,  the 
"premortal  rise"  it  has  been  termed.  The  increased  com- 
bustion of  the  protein  is  due  to  the  requirement  for  energy  in 
an  organism  which  has  a  constantly  decreasing  amount  of 
fat  upon  which  to  draw. 

Zuntz1  describes  a  dog  which  lived  in  a  constant  state  of 
undernutrition  for  about  a  year.  The  energy  requirement 
was  as  follows: 

Weight,  Calories  Per 

Kg.  Square  Meter. 

Start 10  931 

Eleventh  month 4.98  631 

Twelfth  month 4.1  921 

Though  the  nitrogen  in  the  urine  was  not  collected,  Zuntz 
considers  it  possible  that  with  the  utilization  of  body  fat  the 
metabolism  of  protein  increased,  and  therefore  the  heat  pro- 
duction increased  (see  p.  238)  toward  the  end  of  life. 

1  Zuntz:   "Biochem.  Zeitschr.,"  1913,  lv,  341. 


102  SCIENCE    OF   NUTRITION 

The  actual  loss  of  body  weight  is  greater  when  protein  is  the 
source  of  energy  than  when  the  energy  is  derived  from  fat. 
The  metabolism  of  protein  in  ioo  grams  of  flesh  yields  only 
80  calories  in  contrast  with  930  calories  liberated  when  100 
grams  of  fat  are  oxidized.  To  obtain  equivalent  amounts  of 
energy  there  must,  therefore,  be  a  destruction  of  eleven  and  a 
half  times  more  "flesh"  by  weight  than  fat. 

Rubner1  has  maintained  a  dog  for  a  long  period  on  a  diet  of 
fat  which  was  sufficient  in  amount  to  cover  the  energy  require- 
ment. The  content  of  body  nitrogen  fell  from  358.3  grams  to 
166  grams,  a  loss  of  53.7  per  cent.  Rubner  finds  that  during 
the  whole  period  the  daily  waste  of  nitrogen  is  0.9  gram  per  100 
grams  contained  in  the  body.  This  "wear  and  tear"  quota  is 
therefore  a  function  of  the  intensity  of  the  life  processes,  being 
proportional  to  the  amount  of  protoplasmic  material  present. 

What  is  the  cause  of  death  from  starvation?  It  does  not 
seem  to  be  due  to  an  essential  change  in  the  composition  of  the 
cells  themselves,  for  no  chemical  alteration  has  been  detected 
in  them.2  What,  then,  is  the  cause  of  death?  The  general 
argument  of  E.  Voit  is  as  follows:  It  must  be  due  either  to  a 
general  failure  of  all  the  cells  or  injury  of  certain  organs  which 
are  necessary  for  life.  If  the  first  cause  were  the  true  one, 
then  death  would  take  place  when  a  certain  definite  percentage 
of  protein  loss  occurred.  This  does  not  happen,  since  the  body 
loss  at  the  time  of  death  may  vary  between  20  and  50  per  cent, 
of  its  original  protein  content.  When  the  genital  organs  of  the 
salmon  develop  at  the  expense  of  the  liquefying  muscle  sub- 
stance brought  them  by  the  blood,  not  a  single  muscle  cell  of 
the  fish  is  killed,  even  though  these  lose  55  per  cent,  of  their 
protein  in  the  process  (Miescher).  It  seems  extremely  im- 
probable, then,  that  a  much  smaller  loss  of  protein  in  starva- 
tion can  be  the  cause  of  general  cellular  death.  On  the  other 
hand,  if  death  be  due  to  the  failure  of  certain  organs  especially 
important  to  life,  the  cause  is  to  be  found  in  two  factors: 

1  Rubner:    "Archiv  fur  Hygiene,"  1908,  lxvi,  49. 

2  Abderhalden,  Bergell,  and  Doerpinghaus:  "Zeitschrift  fur  physiologische 
Chemie,"  1904,  xli,  153. 


STARVATION 


IO3 


Either  these  organs  receive  too  little  nutrition  for  their 
proper  functioning,  or  they  become  so  emaciated  that  they 
fail  in  spite  of  sufficient  nutriment.  Either  the  fuel  is  in- 
sufficient or  the  machine  wears  out. 

The  following  table  gives  some  answer  to  this.  The  general 
arrangement  is  in  the  order  of  the  greater  original  fat  content 
of  the  animals: 

INFLUENCE  OF  FAT  CONTENT  ON  PROTEIN  METABOLISM  AND 
ON  LENGTH  OF  LIFE   IN  STARVATION 


Animal. 

First 

Weight, 

Kg. 

Fat  in  %. 

Loss  IN  %. 

Days  Be- 
fore Death 
from  Star- 
vation. 

Author. 

Start 

End. 

Animal. 

Body  N. 

Dog 

20.64 

1-95 
0.67 

23-05 
1. 00 

i-5i 

2-53 
2-34 
1.89 

2.08 
2.99 

19 
26 
16 
11 

9.1 

7-i 

6-3 

6-3 

2.7 

2-3 
2-3    ' 

12 

5 
10 

i-7 
0.7 

0.4 

o-5 
0.5 
0.7 
0.4 
0.3 

28 
42 
38 
34 
39 
49 
44 
4i 
34 
35 
32 

22 
26 
26 
35 
37 
49 
49 
45 
4i 
38 
35 

30 

35 
10 

38 
12 

19 

19 

19 

9 

8 

9 

Falk. 

Fowl 

Schmanski. 

Guinea-pig 

Dog 

Rubner. 
Schbndorff. 

Fowl 

Kuckein. 

Rabbit 

Rubner. 

Rabbit 

Koll. 

Rabbit 

Rubner. 

Fowl 

Kuckein. 

Rabbit 

Kaufman. 

Rabbit 

Rubner. 

In  the  first  three  animals  a  large  amount  of  fat  was  present 
at  the  time  of  death,  and  this  had  prevented  a  great  tissue 
waste.  Abundant  food  was  therefore  available  for  the  cells. 
The  cause  of  death  seems,  therefore,  to  be  due  to  a  reduction 
of  activity  in  one  or  more  organs  important  for  life. 

Again,  if  the  protein  loss  be  kept  down  by  administering 
protein  in  quantity  insufficient  for  the  heating  demands  of  the 
organism,  the  animal  is  kept  living  largely  on  his  own  fat. 
Schulz1  in  this  way  kept  two  dogs  alive  for  twenty-eight  and 
thirty-eight  days,  with  losses  of  body  nitrogen  amounting  to 
only  18  and  7  per  cent,  of  the  original  quantity.  The  fat 
present  was  only  0.4  to  0.5  per  cent,  at  the  end.  These  dogs 
certainly  suffered  from  no  general  loss  of  cell  tissue.  E.  Voit 
concludes  that  death  from  starvation  is  primarily  due  to  loss  of 

1  Schulz:   "Pfliiger's  Archiv,"  1899,  lxxvi,  379. 


104  SCIENCE   OF   NUTRITION 

substance  in  organs  important  to  life,  but  it  may  also  ensue  under 
certain  circumstances  as  a  result  of  deficient  nutrition  to  these 
organs. 

Schulz1  and  his  pupils  let  a  dog  which  was  fat  and  well 
nourished  fast  for  twenty-seven  days.  On  the  twenty-fifth  day 
the  animal  manifested  weakness,  which,  on  the  twenty-seventh 
day,  appeared  to  threaten  its  life.  Then  for  a  day  400  c.c.  of 
milk  were  given  to  the  dog  and  on  four  subsequent  days  300 
grams  of  meat  each  day.  Although  these  quantities  of  food 
were  greatly  under  the  quantity  required  to  maintain  the  dog 
without  loss  of  body  fat,  still  the  animal  recovered  its  strength, 
added  7.3  grams  of  protein  nitrogen  to  its  body,  and  then  lived 
during  a  second  period  of  sixty-one  days  of  starvation.  Dur- 
ing this  second  fasting  period  the  protein  metabolism  was  on  a 
much  lower  level  than  during  the  first  period.  Schulz  notices 
that  when  the  fasting  dog  still  contains  considerable  fat, 
protein  in  the  food  is  readily  retained,  even  though  the  content 
of  energy  ingested  be  under  the  body's  needs.  When,  how- 
ever, the  body  fat  is  nearly  exhausted,  all  the  ingested  protein 
and  some  body  protein  besides  is  destroyed  to  provide  for  the 
support  of  the  organism.  Schulz  concluded  that  death  from 
starvation  is  due  to  autotoxemia,  a  condition  which  was 
relieved  in  the  fasting  experiment  mentioned  above  by  the 
ingestion  of  meat. 

On  the  basis  of  their  experiments  Howe  and  Hawk2 
conclude  that  a  "repeated  fast"  is  accompanied  by  less  protein 
loss  from  the  body  than  an  original  fast.  Thus,  in  one  dog 
weighing  originally  3.4  kilograms,  death  was  threatened  after 
15  days  of  fasting,  the  loss  of  body  weight  having  been  45.8 
per  cent.  The  animal  was  then  given  food  for  forty-seven 
days  and  brought  back  to  the  original  weight,  after  which  it 
fasted  again  and  lost  46.8  per  cent,  in  weight  during  thirty 
days.  During  the  first  fast  the  daily  loss  of  body  nitrogen 
was  2.3  grams  and  during  the  second,  1.31  grams. 

1  Schulz:    "Pfluger's  Archiv,"  1906,  cxiv,  419-462. 

2  Howe  and  Hawk:  "Journal  of  the  American  Chemical  Society,"  1911, 
xxxiii,  253. 


STARVATION 


I05 


The  question  of  what  organs  are  attacked  in  starvation  has 
attracted  attention.  Long  ago  Voit1  showed  that  the  muscles 
of  a  cat  which  starved  thirteen  days  lost  30  per  cent.,  while 
heart,  brain,  and  cord  lost  3  per  cent.  only.  In  normally 
nourished  animals  E.  Voit  finds  that  the  relative  weights  of 
the  fat-free  organs  in  animals  of  the  same  species  are  very 
constant.  He2  uses  Kumagawa's3  results  to  show  what 
percentage  the  different  organs  represent  in  the  fat-free 
organism  of  a  dog  before  and  after  a  twenty-four-day  fast. 
The  third  column  represents  the  precentage  loss  of  the  fat-free 
organ  in  starvation: 

LOSS  IN  WEIGHT  OF  DIFFERENT  ORGANS  DURING  STARVATION 


Organ. 

Fat-free  Antmal  Contains  in 
Percentage  of  Weight. 

Fresh  Fat-free 
Organ  Loses  in 

Percentage 

Well  Nourished. 

Starvation. 

Weight  During  a 
24  Days'  Fast. 

Skeleton 

Skin 

14.78 
IO.30 

53-77 
0.94 
0.1 1 

o.54 
7.14 

o-39 
3-98 
°-33 
0.66 
0.30 
5.8i 
0.89 

21.50 

II.29 

48.39 
I. II 
O.16 
O.69 
5-69 
O.26 

3-°5 
O.19 

0.45 
O.23 
6.02 
O.97 

5 
28 

42 

Brain  and  cord 

22 

3 
16 

48 

Heart 

Blood  

Spleen 

57 
50 
62 

Liver 

Kidney 

55 
49 
32 
29 

Genitals 

Stomach  and  intestine .  .  . 
Lungs 

It  is  apparent  that  the  greatest  loss  is  from  the  glands  and  the 
least  from  the  skeleton.  The  activity  of  the  glands  is  greatly 
reduced  in  starvation.  Luciani  found  that  there  was  no 
gastric  juice  formed  during  Succi's  thirty-day  fast,  but  Langley 
and  Edkins4  find  pepsinogen  stored  within  the  cells  of  a  cat's 
gastric  glands.     The  bile  flow  continues  up  to  the  death  of  the 

1  Voit:    "Zeitschrift  fur  Biologie,"  1866,  ii,  353. 

2  E.  Voit:   Ibid.,  1905,  xlvi,  195. 

s  Kumagawa:  "  Aus  den  Mittneil.  d.  med.  Fakultat  der  kais.  Japan.  Univ.," 
Tokio,  1894,  iii,  11. 

4  Langley  and  Edkins:  "Journal  of  Physiology,"  1886,  vii,  371. 


io6 


SCIENCE    OF   NUTRITION 


person,  but  in  diminished  quantity,  corresponding  to  the  lack 
of  food  and  the  decreasing  size  of  the  liver.  The  writer1  has 
noticed  a  great  reduction  in  the  activity  of  the  milk  secretion 
in  starving  goats,  there  being  a  permanent  cessation  of  flow 
after  five  days.  The  percentage  of  fat  increases  in  the  milk, 
as  it  does  in  the  blood,  liver,  and  other  organs.2  The  fasting 
organs  attract  fat  from  the  fat  deposits  of  the  body,  and  it  is 
brought  to  them  by  the  circulating  blood.  Glucose  is  present 
in  the  blood  up  to  the  last  day  of  life,  having  its  probable 
origin  in  a  constant  production  of  sugar  in  protein  metabolism. 
The  composition  of  the  plasma  of  the  blood  in  fasting,  as  re- 
gards its  protein  constituents,  varies  slightly  from  the  normal. 
Lewinski3  gives  the  following  comparative  analyses  of  blood- 
plasma  of  dogs: 

100   C.C.   BLOOD-PLASMA   CONTAIN   OF   GRAMS   N: 


Dog  I. . 
Dog  II. 


Dor  III! 


Dog  IV. 


/Fasting, 
\Fed._. .. 
Fasting 
Fed.... 
f  Fasting 
j  Fed.... 
1  Fasting 
Fasting 
Fed. . . . 


Total. 

Albumin. 

Globulin. 

°-935 

0.621 

0.257 

0.831 

0.5  1 1 

0.240 

0.921 

0-3I3 

0-544 

1.062 

0-SI5 

0.423 

1. 010 

0.467 

0.450 

0.977 

0-475 

0.402 

1.096 

0-554 

0.443 

1.052 

0.536 

0.324 

0.877 

0.542 

0.248 

Fibrin- 
ogen. 


0.057 
O.080 
0.064 
0.124 
O.093 
0.1 00 
0.099 
0.192 
0.087 


The  only  constant  change  seems  to  be  a  slight  increase  of 
globulin  during  fasting.  Burckhardt  believes  this  to  be  due  to 
the  passage  of  globulins  from  the  tissues  to  the  blood.  Robert- 
son4 reports  that  in  the  fasting  dog  and  cat  the  globulins  tend 
to  increase  in  the  blood,  whereas  in  the  rabbit,  ox,  and  horse 
the  albumins  increase.  The  percentage  of  hemoglobin  and  the 
number  of  blood-corpuscles  are  not  appreciably  affected. 
It  is  evident,  then,  that  the  blood  in  starvation  retains  the 

1  Lusk:   Voit's  Festschrift,  "Zeitschrift  fur  Biologie,"  1901,  xlii,  41. 

2  Rosenfeld,   "Ergebnisse  der  Physiologie,"  1903,  ii,  1,  50. 

3  Lewinski:    "Pfliiger's  Archiv,"  1903,  c,  631. 

4  Robertson:   "Journal  of  Biological  Chemistry,"  191 2,  xiii,  325. 


STAEVATION  107 

normal  composition  as  regards  its  nutrient  materials,  except 
that  it  carries  fat  in  increased  quantity  to  the  cells.  In  gen- 
eral the  cells  are  well  nourished  for  the  ordinary  maintenance 
of  the  life  functions.  Hence  the  appetite  is  not  an  expression  of 
general  cellular  hunger,  but  rather  the  result  of  a  local  condi- 
tion of  the  gastro-intestinal  canal,  which  stimulates  the  in- 
dividual to  replenishment. 

The  glycogen  of  an  animal  is  greatly  reduced  during  star- 
vation, but  after  seventy-three  days  it  is  not  entirely  removed.1 
Prausnitz2  reports  that  a  dog  weighing  22  kilograms,  after 
fasting  for  twelve  days  and  after  excreting  287  grams  of  sugar 
in  the  urine  as  the  result  of  phlorhizin  injections,  still  contained 
25  grams  of  glycogen  in  his  body.  The  writer3  has  found  0.4 
gram  of  glycogen  in  the  liver  of  a  meat-fed  phlorhizinized 
dog  after  eleven  days  of  diabetes  and  an  excretion  of  over  600 
grams  of  sugar.  Exercise  will  greatly  reduce  the  glycogen 
content,  but  the  only  method  of  completely  freeing  the 
organism  of  glycogen  is  by  tetanus.4  Zuntz5  rid  a  rabbit  of 
glycogen  by  strychnin  convulsions  and  then  kept  the  rabbit 
fasting  and  under  the  influence  of  chloral  for  119  hours.  Dur- 
ing this  time  5.25  grams  of  sugar  were  excreted  in  the  urine,  and 
yet  1 .286  grams  of  glycogen  were  found  in  the  liver  and  muscles. 
This  must  have  gradually  arisen  from  the  protein  metabolism. 
The  writer6  made  an  observation  that  in  a  fasting  diabetic 
rabbit  tetanus  produced  an  extra  elimination  of  sugar  in  the 
urine  of  1.1  grams,  which  undoubtedly  was  derived  from 
the  glycogen  content  of  the  organism  (see  p.  458)-.  The 
quantity  eliminated  corresponded  to  the  amount  found  as 
glycogen  by  Zuntz,  as  above  mentioned. 

There  now  remains  a  discussion  of  the  influence  of  work 
and  of  change  in  temperature  upon  the  fasting  organism. 

^fliiger:   "Pfliiger's  Archiv,"  1907,  cxix,  119. 

2  Prausnitz:   "Zeitschrift  fur  Biologie,"  1892,  xxix,  168. 

3  Reilly,  Noian,  and  Lusk:   "American  Jour,  of  Physiol.,"  1898,  i,  397. 

4  Kiilz:   Ludwig's  Festschrift,  1891,  p.  119. 

8  Zuntz:  Verhandl.  der  physiol.  Ges.  zu  Berlin,  "Arch,  fur  Physiol.,"  1893, 
P-  378. 

6  Lusk:   "Zeitschrift  fur  Biologie,"  1898,  xxxvi,  in. 


io8 


SCIENCE   OF   NUTRITION 


Frentzel1  has  shown  the  effect  of  external  work  upon  the 
protein  metabolism  of  fasting  dogs.  One  of  the  dogs  did  an 
amount  of  work  corresponding  to  216,937  kilogrammeters  in 
three  days.  The  protein  metabolism  rose  during  the  working 
hours  and  continued  high  on  the  last  day,  which  was  one  of 
complete  rest.  Frentzel  computes  that  the  nitrogen  elimina- 
tion of  the  last  four  days  (=  20.7  grams)  represents  an  energy 
equivalent  of  220,300  kilogrammeters.  This  could  not  cover 
the  work  done  by  the  dog  if  we  add  to  the  measured  work  that 
which  was  done  by  the  heart  and  respiratory  muscles.  The 
protein  metabolism  of  four  days  is  therefore  entirely  insufficient 
to  cover  the  work  done  during  three.  The  source  of  the 
energy  for  the  work  accomplished  must  be  found  in  an  in- 
creased metabolism  of  fat.  The  increase  in  protein  metabo- 
lism above  that  of  rest  was  not  sufficient  to  supply  7  per  cent, 
of  the  energy  needed  to  do  the  work.  The  record  of  the  dog's 
nitrogen  metabolism  is  as  follows: 


INFLUENCE   OF  WORK  ON  THE   N  METABOLISM   OF  FASTING 

DOGS 


Day. 


1st  to  4th 

5th 

6th 

7th 

8th 

9th 

10th 

nth 

1 2th 


Work 
or  Rest. 


Rest. 
Rest. 
Rest. 
Rest. 
Rest. 

Work. 

Work. 

Work. 
Rest. 


Food. 


100  g.  lard 
ioog.    " 
ioog.    " 
Fasting. 


Grams  of  N  Excreted. 


Per  Day.       Per  Hour. 


3-13 

3-52 
3-7i 
3-99 

4-97 
5.02 

5-63 
5.08 


0.1304 

0.1467 

0.1546 

0.1663 

0.3680* 

o.i837t 

0.2750* 

o.i96of 

0.2400* 

°.2335f 
0.2117 


Work. 


t  Rest. 


Succi  did  not  show  a  similar  rise  of  protein  metabolism 
from  the  effect  of  work.     The  eleventh  day  of  his  fast  he  spent 

1  Frentzel:    "Pfliiger's  Archiv,"  1897,  lxviii,  212. 


STARVATION 


IO9 


in  bed.  On  the  twelfth  day  he  rode  a  horse  for  an  hour  and 
forty  minutes,  raced  for  eight  minutes  with  some  students,  and 
gave  an  exhibition  of  fencing  in  the  evening.  During  the  day 
he  walked  19,900  steps.  The  urinary  nitrogen  on  the  eleventh 
day  (rest)  was  7.88  grams;  on  the  twelfth  (work),  7.16;  and 
on  the  days  following  3.50,  5.33,  5.14,  5.05.  The  work  done 
was  evidently  at  the  expense  of  increased  metabolism  of  fat. 
That  this  is  the  case  had  already  been  demonstrated  by 
Pettenkofer  and  Voit.1  A  fasting  man  at  work  showed  no 
increase  in  his  protein  metabolism,  but  the  quantity  of  fat 
burned  rose  enormously.  This  is  shown  by  the  following 
comparison  of  the  number  of  grams  of  fat  burned: 


Day  Night. 

8  a.  m.  to  8  p.  m.  8  P.  m.  to  8  A.  M. 


Rest  during  day 116  gm.  94  gm. 

Work  during  nine  hours  of  day  period . .  312  gm.  70  gm. 


The  fat  metabolism  during  the  day  of  work  is  two-and-a- 
half  times  that  of  the  resting  day,  and  is  presumably  the  source 
of  the  energy  for  the  mechanical  work  accomplished.  During 
the  night  following  the  working  day  the  reduction  of  fat 
combustion  as  compared  with  the  night  before  is  due  to  more 
profound  sleep. 

Another  phase  of  the  effect  of  work  is  shown  in  the  variation 
between  the  day  and  night  metabolism  of  Tigerstedt's  fasting 
medical  student,  J.  A.  The  average  carbon  dioxid  excretion  in 
grams  for  two-hour  periods  during  five  days  of  fasting  was  as 
follows.  The  figures  showing  the  elimination  during  the  hours 
of  sleep  are  printed  in  black : 

A.  m.  p.  M. 

Time 10-12    12-2      2-4      4-6       6-8      8-10    10-12 

Carbon  dioxid  (grams)...  .      54.8      57.2      54.1      57.8      59.5      66.4     46.5 

A.M. 

Time 1 2-2      2-4      4-6       6-8 

Carbon  dioxid  (grams) 37.5      39.1      40.7      68.6 

1  Pettenkofer  and  Voit:  "Zeitschrift  fur  Biologie,"  1866,  ii,  459;  C.  Voit: 
Ibid.,  1878,  xiv,  144. 


no 


SCIENCE   OF   NUTRITION 


The  nitrogen  of  the  urine  was  also  less  during  sleep  than 
during  the  waking  hours: 


N  in  the  Urine. 


Fasting  Day. 


ist 
2d. 
3d. 
4th 
5th 


Johansson1  finds  that  the  inequality  of  night  and  day 
metabolism  depends  on  muscular  work.  Sitting  up  raises  the 
metabolism,  and  standing  does  so  still  more.  Even  when  one 
lies  in  bed,  restlessness  during  the  day  may  increase  the 
metabolism.  Zuntz2  was  the  first  to  mention  the  condition 
of  absolute  muscular  rest  as  significant.  Even  when  perfect 
muscular  relaxation  ensues  there  may  still  be  influences,  such 
as  fight  on  the  retina  or  sounds,  which  may  act  reflexly  on  the 
organism  and  slightly  increase  the  metabolisp.  Johansson 
illustrated  these  variations  in  the  following  comparisons 
between  night  and  day  excretion  of  carbon  dioxid  of  starving 
men,  the  night  C02  being  figured  at  ioo: 


Complete  muscular  rest 

Ordinary  rest  in  bed 

Ordinary  life  (no  hard  work) 


Night  COs. 

Day  C02. 

ioo 

1 05 

IOO 

no 

IOO 

142 

IOO 

128 

IOO 

147 

Author. 


Johansson. 

Johansson. 

Tigerstedt. 

PettenkoferandVoit. 

Tigerstedt. 


Johansson  agrees  with  Tigerstedt  that  the  minimum 
metabolism  of  a  man  in  bed  is  represented  by  24  to  25  calories 
per  kilogram  daily,  and  results  obtained  by  Zuntz,  Loewy, 
and  others  lead  to  the  same  conclusion.3 

1  Johansson:    "Skan.  Archiv  fur  Physiologie,"  1898,  viii,  109. 

2  Lehmann  and  Zuntz:    "Virchow's  Archiv,"  1893,  cxxxi,  Supplement,  26. 

3  Tigerstedt:    "Skan.  Archiv  fur  Physiologie,"  1910,  xxiii,  302. 


STARVATION 


III 


The  temperature  of  the  fasting  organism  is  usually  normal. 
Luciani  found  a  normal  temperature  in  Succi  during  his  thirty- 

Crams  COz 

her  hour 
35 


30 


Z5 


10 


10 


, — 1 

6 

f 

/ 

»i 

> 

\t 

,    i 

* 

< 

J 

/ 

0 

/ 

2 

; 

l. 

t 

6 

3r 

Temp. 
5? 


Sleep 


iVoon. 


Fig.  s. — Curve  of  carbon  dioxid  elimination  compared  with  Jurgensen's 
curve  of  normal  diurnal  temperature  variation.  This  individual  led  a  normal 
life  and  partook  of  his  usual  nourishment. 

day  fast.     The  temperature  falls  only  a  few  days  before  death. 
Sonden  and  Tigerstedt1  find  that  the  diurnal  variations  persist 

1  Sonden  and  Tigerstedt:  "Skan.  Archiv  fur  Physiologie,"  1895,  vi,  136. 


112 


SCIENCE   OF   NUTRITION 


during  fasting  in  their  ordinary  rhythm.  The  average 
temperature  of  the  medical  student  J.  A.  during  his  five-day 
fast  was  but  0.16  degree  below  his  normal  temperature  when 
food  was  allowed  him.  These  diurnal  variations  are  exactly 
concomitant  with  the  fluctuations  of  carbon  dioxid  excretion 
noted  on  a  previous  page.  When  the  carbon  dioxid  produc- 
tion increases,  the  temperature  rises. 


Grams  CO  l 

btrtwar 

ZSq. 


Z0$. 


1 — 1 

1 

, 

iZ       z 


sr 

Temf> 
36' 


Noon. 


M'jkt 


Fig.  6. — Carbon  dioxid  elimination  and  body  temperature  in  fasting  and  com- 
plete muscular  rest. 


This  parallelism  may  be  easily  shown  by  comparing  the 
two  factors  in  the  chart  (Fig.  5)  as  given  by  Sonden  and 
Tigerstedt.1  Furthermore,  the  diurnal  variations  tend  to 
disappear  if  the  person  be  kept  in  a  state  of  muscular  rest,  so 

1  Sond6n  and  Tigerstedt:   Ibid.,  p.  132. 


STARVATION  II3 

that  the  output  of  energy  during  the  day  and  the  night  re- 
mains the  same.  In  this  state  the  temperature  may  fall  0.6 
degree  below  the  normal  on  account  of  the  absence  of  muscle 
movement.  This  regularity  of  temperature  and  metabolism 
is  beautifully  shown  in  Fig.  6  taken  from  Johansson.1 

Inversion  of  the  normal  routine  of  life,  so  that  one  sleeps  in 
the  daytime  and  is  awake  and  active  at  night,  brings  about  an 
inversion  of  the  curve  of  body  temperature.  This  is  well 
shown  in  the  monkey.2 

Benedict,3  however,  was  unable  to  obtain  any  inversion  of 
the  curve  of  normal  body  temperature  in  men  who  worked 
during  the  night  and  slept  during  the  day. 

Gibson4  traveled  half-way  round  the  world  in  making  a 
trip  from  New  Haven,  Connecticut,  to  Manila,  and  then  re- 
turned. He  found  that  the  rhythm  of  daily  variation  was 
dependent  on  the  time  of  the  solar  day  and  was  independent  of 
the  part  of  the  world  in  which  he  happened  to  be. 

1  Johansson:   Loc.  cit.,  p.  142. 

2  Galbraith  and  Simpson:  Proceedings  of  the  Physiological  Society,  "Jour, 
of  Phys.,"  1904,  xxx,  p.  xx. 

3  Benedict:    "  Amer.  Jour,  of  Phys.,"  1904,  xi,  145. 

4  Gibson:  "Amer.  Jour,  of  Med.  Sci.,"  1905,  cxxix,  1049. 


CHAPTER  IV 


THE  REGULATION  OF  TEMPERATURE 

It  has  been  seen  that  the  temperature  of  a  warm-blooded 
animal  is  maintained  at  the  normal  throughout  a  fast.  Not 
only  this,  but  it  is  maintained  at  the  same  level,  even  though 
the  temperature  of  the  outside  environment  vary  from  o°  C.  and 
lower  to  300  to  350  C.  In  cold-blooded  animals  the  temperature 
of  the  body  is  only  slightly  higher  than  that  of  their  environ- 
ment at  the  time.  The  metabolism  of  such  animals  varies 
with  the  temperature.  The  frog  in  the  mud  during  the  winter 
at  a  temperature  of  40  C.  has  quite  a  different  metabolism 
from  that  which  he  enjoys  during  the  summer  sunshine  as  he 
sits  on  the  river-bank  or  snaps  at  passing  flies.  The  curve  of 
his  carbon  dioxid  elimination  at  various  temperatures  has  been 
made  by  E.  Voit  from  the  analyses  of  H.  Schulz,1  and  is 
given  below : 

COz  innf. 
fr°2  AOC 


300 


400 
300 
200 
100 


If  20'  3<r         Temjb. 

Fig.  7. — COo  in  milligrams  per  hour  per  kg.  frog. 

Krogh2  finds  that  the  rise  in  the  metabolism  of  the  normal 
frog  which  appears  at  200  C.  does  not  show  as  sharp  an  ascent 

1  Schulz:    "Pfluger's  Archiv,"  1877,  xiv,  78. 

2  Krogh:    "Internat.  Zeitschr.  f.  physik.-chem.  Biologie,"  1914,  1,  492. 

114 


THE   REGULATION   OF   TEMPERATURE 


115 


in  narcotized  animals,  indicating  that  in  the  normal  frog  ner- 
vous influences  which  produce  tone  begin  to  make  themselves 
felt  at  this  temperature. 

Rohrig  and  Zuntz1  first  showed  that  a  curarized  mammal 
at  ordinary  room  temperature  lost  the  power  of  maintaining 
its  body  temperature,  and  the  intensity  of  its  metabolism 
decreased  accordingly.  Curare  prevents  the  transmission  of 
motor  impulses  to  voluntary  muscles. 

Krogh  states  that  the  curve  of  oxygen  absorption  as  in- 
fluenced by  body  temperature  is  the  same  in  the  anesthetized 

ccG^per 

minute 


1      )  — r 


1 1 1 r 


2  _  +- 


/v 


20* 


JO' 


W* 


Fig.  8. — Curve  of  metabolism  of  a  curarized  dog  subjected  to  different  tem- 
peratures (after  Krogh). 

frog  and  fish  as  in  the  curarized  dog.  One  of  Krogh's  curves 
which  is  given  here  shows  a  sixfold  increase  of  oxygen  ab- 
sorption in  the  curarized  dog,  indicated  by  a  rise  from  2.1  c.c. 
per  minute  at  a  body  temperature  of  140  C.  to  13  c.c.  per 
minute  when  the  body  temperature  reached  37.20  C. 

If  the  sciatic  nerves  of  a  curarized  dog  be  severed,  Mans- 
field and  Lukacs2  found  that  the  heat  production  falls  10  or  15 
per  cent.,  but  if  the  sympathetic  nerves  had  previously  been 
severed,    cutting    the    sciatic    was    without    influence    upon 


1  Rohrig  and  Zuntz:    "Pfliiger's  Archiv,"  1871,  iv,  57. 

2 Mansfield  and  Lukacs:    "Pfliiger's  Archiv,"  1915,  clxi,  467. 


Il6  SCIENCE   OF    NUTRITION 

metabolism.  From  this  they  conclude  that  in  the  curarized 
animal  sympathetic  nerves  carry  impulses  which  produce 
tone  in  muscles. 

The  reduction  in  activity  which  accompanies  reduced  body 
temperature  is  exemplified  by  the  fact  that  a  cat  whose  tem- 
perature has  been  artificially  reduced  to  190  C.  may  have  but 
one  heart-beat  per  minute.1  At  the  time  of  hibernation  the 
marmot  lives  at  the  expense  of  fat.  The  metabolism  may 
correspond  to  only  one-thirtieth  the  amount  of  energy  used 
during  the  period  of  activity.2 

Henriques3  reports  concerning  the  metabolism  of  a  hedge- 
hog awakening  from  the  winter  sleep.  The  animal  weighed 
660  grams.  Tracheotomy  was  performed  and  the  respiratory 
exchange  determined  during  half-hour  periods  with  five-minute 
intervals  between  periods,  by  the  Zuntz  method.  The  animal's 
body  temperature  was  6.50  C.  in  the  rectum  at  the  start,  and 
the  room  temperature  was  130  C.  The  animal  remained 
quiet  except  for  characteristic  muscle  movements  resembling 
shivering  which  always  accompany  the  awakening  of  hibernat- 
ing animals. 

The  results  were  as  follows: 

Period.  I.  II.  III.  IV.  V. 

R.  Q 0.62  0.70  0.72  0.71  0.70 

Oxygen,  c.c,  hour  and  kg..  375  334  851  1983  2083 

Rectal  temperature  at  end  7.50  o.o°  10. 70  14.10  26. 6°  C. 

Contrary  to  other  authors,  Henriques  concludes  that  the 
awakening  from  winter  sleep  is  usually  at  the  expense  of  fat 
and  not  of  carbohydrate. 

During  the  entire  period  2.21  liters  of  oxygen  were  ab- 
sorbed by  the  animal.  If  this  had  been  used  for  the  oxidation 
of  fat  the  heat  produced  would  have  been  10.40  calories  (2.21  X 
4.7  cals.,  see  p.  61).  At  the  conclusion  of  the  experiment  the 
animal  was  killed  and  placed  in  an  ice  calorimeter.  It  was 
found  that  the  whole  animal  gave  off  13.41  calories.     At  the 

1  Simpson  and  Herring:    "Journal  of  Physiology,"  1905,  xxxii,  305. 

2  Regnault  and  Reiset:    "  Annales  de  chem.  et  de  physic,"  1849,  xxvi,  299. 

3  Henriques:   "Skan.  Archiv  f.  Physiol.,"  1911,  xxv,  15. 


THE  REGULATION  OF  TEMPERATURE         117 

beginning  of  the  experiment  when  the  rectal  temperature  was 
6. 50  C.  the  hedgehog  contained  3.56  calories  (6.50  C.  X  660 
grams  X  0.83  factor  for  specific  heat  of  body).  Therefore  9.85 
calories  were  added  to  the  body  during  the  period  of  awaken- 
ing, and  these  could  have  been  obtained  from  the  10.40  calories 
derived  from  oxidation  of  fat  and  still  leave  a  surplus  of  0.55 
calorie  for  loss  of  heat  through  radiation  and  conduction  during 
the  period  when  the  body  temperature  was  above  the  temper- 
ature of  the  environment.  It  should  be  remembered,  how- 
ever, that  during  the  earlier  periods  of  low  body  temperature 
the  organism  must  have  gained  heat  from  its  environment. 

E.  Voit1  has  drawn  attention  to  the  fact  that  a  curve  of 
increasing  metabolism  with  increasing  temperature  corresponds 
to  the  increasing  ability  of  muscle  to  contract,  and  to  the 
increasing  effectiveness  of  enzymotic  activity.  A  high  tem- 
perature is  necessary  for  the  irritability  and  activity  of  pro- 
toplasm. The  warmth  of  the  sunshine  increases  the  irri- 
tability of  the  protoplasm  of  the  tree  in  the  spring,  with  the 
resulting  development  of  the  foliage.  Warmth,  however,  is 
not  the  cause  of  the  metabolism,  but  only  one  of  the  conditions  for 
it.  In  warm-blooded  animals  the  temperature  is  maintained 
at  a  constant  level  independent  of  climatic  conditions,  and 
this  level  is  a  favorable  one  for  the  activity  of  nerve  and  muscle. 
It  would  indeed  be  inconvenient  were  the  active  life  of  a  man 
dependent  upon  the  temperature  of  his  environment.  The 
essential  mechanism  for  the  regulation  of  the  body  temper- 
ature is  nervous.  The  action  of  cold  on  the  skin  may  stim- 
ulate its  peripheral  nerve-endings,  which  are  sensitive  to 
cold,  and  reflexly  effect  in  the  organism  a  greater  heat  pro- 
duction and  a  vasoconstriction  of  peripheral  blood-vessels; 
the  action  of  heat,  on  the  contrary,  effects  vasodilatation  and 
production  of  sweat.  It  is  believed  that  the  cold-blooded 
progenitors  of  warm-blooded  animals  changed  their  habitat 
from  the  sea  to  the  land  at  a  tropical  temperature  which  is  at 
present  possessed  by  their  descendants.     In  the  course  of 

1  E.  Voit:  " Sitzungsber.  der  Ges.  fur  Morph.  und  Physiol.,"  1896.  Heft  III. 


Il8  SCIENCE    OF   NUTRITION 

development  these  animals  acquired  the  power  to  maintain 
that  ancestral  temperature  which  proved  favorable  for  the 
activity  of  their  body  substance.  The  nervous  mechanism 
through  which  this  is  accomplished  is  twofold:  First,  there  is 
an  increased  production  of  heat  in  the  presence  of  external 
cold  {the  chemical  regulation  of  temperature);  and,  second, 
variations  in  the  quantity  of  blood  supplied  to  the  skin  modify 
loss  of  heat  by  radiation  and  conduction,  and  variations  in  the 
amount  of  sweat  modify  the  loss  of  heat  by  evaporation  of 
water  (these  are  the  factors  of  the  physical  regulation  of  tem- 
perature). The  great  importance  of  these  two  controlling 
influences  will  be  seen  as  the  subject  develops. 

If  the  body  were  a  mass  of  cells  having  the  shape  of  a  ball 
with  a  constant  heat  production  in  its  center,  it  would  be  easy 
to  calculate  its  temperature  in  the  different  zones  of  the  inte- 
rior. The  loss  of  heat  from  the  surface  would  obviously  be 
equal  to  the  heat  production  if  the  temperature  of  the  various 
zones  continued  constant. 

If  two  balls  of  the  same  material,  but  of  unequal  size,  were 
equally  warm,  the  smaller  would  cool  more  quickly  than  the 
larger  on  account  of  the  relatively  greater  exposed  surface 
from  which  heat  could  be  discharged.  The  heat  elimination 
would  be  proportional  to  the  surface  exposed. 

To  determine  the  surface  of  geometrically  similar  solids, 
and  hence  of  animals  of  similar  shapes,  the  following  formula 
was  used  by  Meeh,1  in  which  S  =  surface  and  V  =  volume: 

_S_  _  £#V 
V|"     V 

Since  animals  contain  the  same  materials,  one  may  substi- 
tute W  =  weight  for  V. 

Then  the  value  of  ^— —  may  be  empirically  determined 
w 

for  each  shape  or  animal,  and  this  value  =  k.  Hence  the 
formula  would  read: 

-|r  =  k  or  S  =  k^W* 
Wf 

1  Meeh:    "Zeitschrift  fur  Biologie,"  1879,  xv,  425. 


THE    REGULATION   OF   TEMPERATURE  119 

The  value  of  k  or  the  constant  in  the  relationship  of  weight 

in  kilograms  to  surface  in  square  meters  in  each  animal  has 

been  given  by  Rubner  as  follows: 

Man 12.3 

Dog 11. 2-10. 3 

Rabbit 12. 9-1 2.0 

Rabbit  (without  ears) 10.8 

Calf 10.5 

Sheep 1 2.1 

Cat 9.9 

Pig 8.7 

Guinea-pig 8.5 

Fowl 10.4 

Rat 9.1 

White  mouse 1 1 .4 

To  compute  the  body  surface  of  a  man,  for  example,  the 
formula  1 2. 3  f  (body- weight)2  would  be  employed. 

The  use  of  the  above  formula  rendered  possible  the  calcu- 
lation of  the  heat  elimination  per  unit  of  area  in  fasting  animals 
during  periods  of  twenty-four  hours  when  the  temperature  of 
the  environment  is  150  C.  and  when  moderate  voluntary  move- 
ments are  permitted.  When  the  subjects  have  been  previously 
well  fed,  and  are  not  emaciated,  there  is  a  surprising  uniformity 
of  result.  It  is  Rubner's  law  that  the  metabolism  is  pro- 
portional to  the  superficial  area  of  an  animal. 

Erwin  Voit1  has  calculated  the  following  general  table 
showing  the  heat  production  in  resting  animals  of  various  sizes 
at  medium  temperatures  of  the  environment: 

Calories  Produced 

Weight  in  Kg.  Per  Kilo.  Per  Sq.  M.  Surface. 

Horse 441  11.3  948 

Pig 128  19. 1  1078 

Man 64.3  32.1  1042 

Dog.. 15-2  5i-5  1039 

Rabbit 2.3  75.1  776 

Goose 3.5  66.7  969 

Fowl 2.0  71.0  943 

Mouse2 0.018  212.0  1188 

Rabbit2  (without  ears) 2.3  75.1  917 

The  universality  of  this  law  of  Rubner's  is  remarkable. 
Even  at  a  room  temperature  of  300  C.  where  all  thermal  influ- 

1  E.  Voit:   "Zeitschrift  fur  Biologie,"  1901,  xli,  120. 

2  Rubner:   "Energiegesetze,"  1902,  p.  282. 


120  SCIENCE    OF    NUTRITION 

ence  is  removed,  two  guinea-pigs  of  different  sizes  will  produce 
heat  in  proportion  to  their  surface.  In  this  case  there  is  a 
minimum  of  heat  production  determined  for  the  resting  organ- 
ism according  to  the  law  of  superficial  area. 

When  this  discovery  was  first  made,  the  interpretation  was 
offered  that  the  variation  in  the  metabolism  of  different  animals 
in  proportion  to  the  skin  area  was  due  to  the  "chemical 
regulation"  brought  about  by  the  specific  sensory  influences 
of  cold  proceeding  from  a  definite  area  of  surface.  Before 
this  Regnault  and  Reiset  had  noted  that  the  heat  production 
of  sparrows  per  unit  of  weight  was  tenfold  that  of  fowls,  a 
phenomenon  which  they  asserted  was  due  to  the  fact  that  the 
smaller  animals  present  a  relatively  larger  surface  to  the 
surrounding  air  and  thereby  experience  a  considerable  chilling, 
with  the  consequent  generation  of  sufficient  heat  to  maintain 
the  normal  body  temperature.  This  explanation  fell  when 
Rubner  discovered  that  at  a  temperature  of  300  C,  under 
which  condition  all  thermal  stimulus  to  the  organism  ceased, 
two  guinea-pigs  of  different  sizes  still  produced  heat  in  propor- 
tion to  their  skin  areas.  A  similar  fact  was  noted  by  Frank 
and  Voit,1  who  found  that  the  administration  of  curare,  which 
paralyzes  the  voluntary  muscles,  scarcely  affected  the  carbon 
dioxid  output  of  a  dog  as  compared  with  what  was  eliminated 
during  ordinary  muscular  rest,  provided  the  temperature  of 
the  animal  was  maintained  at  the  normal  by  keeping  him  in 
a  warmed  chamber.  The  mass  of  living  cells  preserved  the 
same  metabolism  as  before,  even  though  a  pathway  of  heat 
increase  had  been  cut  off  through  paralysis  by  curare  of  the 
motor  nerve-endings  in  the  muscles.  Keeping  the  animal  in  a 
warmed  chamber  was  necessary  in  this  case,  for  Rohrig  and 
Zuntz2  had  shown  that  curarized  animals  at  the  ordinary  room 
temperature  lost  the  power  of  maintaining  their  body  tem- 
perature and  that  their  metabolism  decreased  accordingly. 
The  removal  of  the  chemical  regulation  caused  a  behavior 

1  Frank  and  Voit:    "Zeitschrift  fur  Biologie,"  1001,  xlii,  309. 

2  Rohrig  and  Zuntz:    "Pfliiger's  Archiv,"  1871,  iv,  57. 


THE  REGULATION  OF  TEMPERATURE         121 

toward  external  temperature  similar  to  that  of  cold-blooded 
animals. 

Although  the  effect  of  cold  on  the  skin  (inducing  chemical 
regulation)  is  of  itself  demonstrably  insufficient  to  account 
for  the  "law  of  skin  area,"  Rubner1  argues  that  even  at  300 
C,  when  the  body  is  losing  heat  by  means  of  the  dilatation  of 
the  blood-vessels  and  the  evaporation  of  water  (physical  reg- 
ulation), the  law  is  still  a  necessity  if  the  general  mechanism 
for  loss  of  heat  in  the  various  animals  is  the  same  in  all.  An 
infant  produces  90  calories  per  kilogram  in  twenty-four  hours; 
an  adult,  32  calories.  Were  the  metabolism  of  an  adult  90 
calories  per  kilogram,  the  means  of  heat  elimination  through 
his  comparatively  smaller  surface  would  have  to  be  materially 
modified  if  a  normal  temperature  were  to  be  maintained  with 
comfort. 

Further  analysis  showed  Rubner2  that  this  evenness  of 
heat  production  per  unit  of  body  surface  was  not  due  to  any 
relation  between  the  area  of  body  surface  and  the  area  of  cell 
surface  within  the  organism. 

Rubner  estimates  that  a  man  weighing  60  kilograms  con- 
tains 37.8  kilograms  of  cell  mass,  of  which  40  per  cent,  is  in 
muscle  tissue,  and  that  while  the  absorptive  surface  of  the 
intestinal  tract  is  1.5  square  meters,  the  surface  area  of  the 
body  cells  amounts  to  9014  square  meters  (2.2  acres).  There 
are  in  1  kilogram  of  body  weight  of  man  150.2  square  meters 
of  such  surface,  and  each  square  meter  of  cell  surface  produces 
at  least  0.2  calorie  per  day.  In  the  newborn  mouse  each 
square  meter  of  cell  surface  produces  eleven  times  this 
amount,  or  2.2  calories.  It  is  of  interest,  also,  to  note  that  a 
kilogram  of  yeast  cells  presents  a  surface  area  of  600  square 
meters  and  at  a  temperature  of  380  C,  or  that  at  which  mam- 
malian cells  exist,  1.25  calories  per  square  meter  of  surface 
are  produced  in  twenty-four  hours,  8.34  grams  of  cane-sugar 
undergoing  inversion  and  fermentation  during  that  interval. 

1  Rubner:   "Energiegesetze,"  1902,  p.  174. 

2  Rubner:    "  Archiv  fur  Physiologic,"  1913,  p.  240. 


122  SCIENCE   OF   NUTRITION 

This  reaction  is  independent  of  the  strength  of  the  sugar 
solution  within  the  wide  limits  of  2.5  to  20  per  cent.  If  the 
strength  of  the  solution  be  at  the  maximum  of  normal  reac- 
tion, or  20  per  cent.,  the  quantity  of  sugar  utilized  in  twenty- 
four  hours  would  be  contained  in  a  film  j^o  millimeter  in 
thickness  surrounding  the  cells.  A  like  analysis  shows  that 
in  man,  whose  cells  are  bathed  in  a  medium  containing  0.1  per 
cent,  of  sugar,  the  quantity  necessary  for  the  support  of  life 
during  one  day  would  be  contained  in  a  layer  which  if  spread 
around  the  cell  would  be  roo  millimeter  in  thickness. 

From  the  calculation  of  the  energy  requirement  in  the  food 
for  the  life  of  a  man  to  the  energy  liberated  by  a  yeast  cell  in 
its  simple  resolution  of  sugar  into  alcohol  and  carbon  dioxid 
is  indeed  a  far  cry,  except  as  showing  that  the  energy  doctrine, 
as  enunciated  by  Rubner,  unites  the  world  of  living  things. 

Magnus-Levy1  made  41  short  time  respiration  experi- 
ments on  the  same  man  when  resting  without  food.  The 
greatest  variations  from  the  mean  were  —7  and  +10  per 
cent.  The  calories  per  square  meter  per  twenty-four  hours 
were  812.  In  1912  Lusk2  calculated  that  the  heat  pro- 
duction of  three  quiet  and  sleeping  dogs  was  759,  748,  and  746 
calories  per  square  meter  of  surface  at  an  environmental  tem- 
perature of  2 6°  C,  that  a  dwarf  produced  775  calories  per 
square  meter  of  surface,  and  that  four  out  of  five  sleeping  men 
investigated  by  Benedict  showed  an  average  heat  production 
of  789  calories  per  unit  of  area.  Only  in  the  sleeping  infant  7 
months  old,  investigated  by  Howland,  did  the  metabolism 
appear  out  of  the  ordinary  and  reached  a  level  of  n 00  calories, 
and  this  factor  was  specifically  pointed  out  as  indicating  a 
higher  metabolism  in  the  youthful  protoplasm  than  is  present 
in  the  adult. 

The  critical  studies  of  F.  G.  Benedict3  led  him  to  conclude 
"that  the  metabolism  or  heat  output  of  the  human  body,  even 

1  Magnus-Levy:   "Pfluger's  Archiv,"  1894,  lv,  1. 

2 Lusk  (with  McCrudden):    "Journal  of  Biological  Chemistry,"  1913,  xiii, 

45°- 

3  Benedict,  F.  G.:    "Journal  of  Biological  Chemistry,"  1915,  xx,  298. 


THE  REGULATION  OF  TEMPERATURE 


123 


at  rest,  does  not  depend  on  Newton's  law  of  cooling,1  and  is, 
therefore,  not  proportional  to  the  body  surface." 

That  a  greater  metabolism  is  induced  in  man  after  the 
ingestion  of  a  liter  of  cold  milk  than  after  taking  the  same 
amount  when  it  is  warm,  was  shown  in  Tangl's2  laboratory,  and 
indicates  that  an  influence  may  be  exerted  by  cooling.  The 
body  temperature  fell  0.25  to  0.8  degree.  That  such  an  influ- 
ence is  exerted  by  cooling  was  clearly  demonstrated  by  Lusk,3 
who  compared  the  heat  production  after  giving  glucose  dis- 
solved in  cold  water  and  in  water  at  the  body  temperature  to 
a  dog  placed  in  a  calorimeter,  with  the  following  results: 


Glucose  in  Cold  Tap-water. 

Glucose  in  Water  at  380  C. 

Indirect. 

Direct. 

Indirect. 

Direct. 

Calories. 
80.33 

Calories. 
75-19* 

Calories. 
75-92 

Calories. 
76.39 

*  Plus  heat  for  warming  the  cold  water. 

When  warm  water  was  ingested  the  computed  heat  production 
agreed  with  that  actually  found,  but  when  cold  water  was 
given  there  was  an  increased  oxidation,  as  shown  by  indirect 
calorimetry,  in  order  to  provide  for  the  body  heat  lost  to  the 
fluid  in  the  stomach  (see  p.  132). 

Benedict  is  in  agreement  with  Carl  Voit  when  he  concludes 
that  the  mass  of  active  protoplasmic  tissue  determines  the 
height  of  the  metabolism.  However,  in  the  search  for  a 
standard  upon  which  to  calculate  what  would  be  the  normal 
heat  production  of  a  man  suffering  from  disease  it  is  ob- 
viously impossible  to  measure  the  mass  of  active  proto- 
plasmic tissue. 

1  This  law  reads,  "The  quantity  of  heat  gained  or  lost  by  a  body  in  a  second 
is  proportional  to  the  difference  between  its  temperature  and  that  of  the  sur- 
rounding medium  "  At  the  higher  temperatures  of  environment  it  is  obvious 
this  law  does  not  control.  See  Rubner's  experiments  on  guinea-pigs,  p.  120, 
demonstrating  that  the  effect  of  cold  on  the  skin  is  not  a  sufficient  explanation 
of  the  law  of  skin  area. 

2  Hari  and  von  Pesthy:    "Biochemische  Zeitschrift,"  1912,  xliv,  6. 

3  Lusk:   "Journal  of  Biological  Chemistry,"  1915,  xx,  578. 


124  SCIENCE    OF   NUTRITION 

When  the  Russell  Sage  Institute  of  Pathology  constructed 
in  Bellevue  Hospital  an  Atwater-Rosa  calorimeter  copied  in 
the  main  after  the  successful  models  of  Benedict,  it  became 
absolutely  essential  that  some  criterion  of  normal  metabolism 
be  established  as  a  basis  from  which  one  could  estimate 
whether  the  metabolism  of  a  patient  under  investigation  was 
higher  or  lower  than  the  normal.  The  severe  criticisms  of 
Benedict  upon  the  method  of  estimating  heat  production  from 
the  unit  of  surface  led  to  a  very  careful  review  of  all  the  evi- 
dence and  to  new  experiments.  Du  Bois,1  who  took  up  this 
work,  has  used  an  accurate  and  ingenious  method  with  which 
he  has  been  able  actually  to  measure  the  surface  area  of  normal 
men.  He  covered  the  body  surface  with  tight-fitting  under- 
wear, applied  melted  paraffin,  and  then  paper  strips  to  prevent 
change  in  area  when  the  covering  was  removed.  This  model 
of  the  surface  when  cut  into  flat  pieces  was  photographed  upon 
paper  in  which  equal  areas  were  of  equal  weight.  From  the 
weight  of  paper  which  received  the  photographic  impression 
the  area  of  body  surface  could  readily  be  calculated.  A 
round  ball  having  an  area  of  0.1490  square  meter,  when 
measured  by  this  method,  gave  an  area  of  0.1488  square 
meter.  After  this  fashion  E.  F.  and  Delafield  Du  Bois  have 
discovered  that  the  formula  heretofore  used  for  estimating 
the  surface  area  in  man  showed  an  average  inaccuracy  of 
16  per  cent,  and  a  maximal  variation  from  the  normal 
of  36  per  cent.,  this  being  found  in  very  fat  individuals. 
Two  new  formulae,  a  "linear"  and  a  "height-weight"  formula, 
have  been  evolved  which  give  an  average  variation  of  ±  1.5 
per  cent,  and  a  maximal  variation  of  ±  5  per  cent.  Using  the 
older  formula  of  Meeh,  the  heat  production  per  square  meter 
of  surface  is  833  calories  during  twenty-four  hours,  but  using 
the  more  accurate  formula  of  Du  Bois  this  rises  16  per  cent, 
to  953  calories.  In  normal  adults  of  various  shapes  and 
sizes  this  is  the  basal  metabolism  as  measured  when  the  individ- 

1  Du  Bois,  D.  and  E.  F.:  "Archives  of  Internal  Medicine,"  1915,  xv,  868; 
Ibid.,  1916,  xvii,  863. 


THE  REGULATION  OF  TEMPERATURE 


125 


ual  is  resting  and  before  the  administration  of  food  in  the 
morning. 

The  following  table  presents  the  results  of  work  upon  those 
persons  whose  surface  areas  were  actually  measured: 

COMPARISON  OF  AREA  OF  BODY  IN  SQUARE  METERS  AS 
ACTUALLY  MEASURED  WITH  THAT  CALCULATED  FROM 
THE   DU   BOIS   FORMULA 


Area. 

Person. 

Meas- 

ured. 

Men: 

Sq.  M. 

Benny  L 

0.8473 

Morris  S 

1.6720 

R.  H.  H 

1.8375 

E.  F.  D.  B.... 

1.9000 

GeraldS 

1.4001 

R.  H.  S 

I.7g8i 

Fabian  S 

1. 1869 

R.  L.  (Legless) 

1.4200 

Women : 

Mrs.  McK... 

1.8592 

Emma  W 

1.6451 

Child: 

Anna  M 

0.3699 

Error    Error 
Area         in      !    with 
Calcu-  DuBoisMeeh's 
lated.      For-       For- 
mula,    mula. 


Sq.  M. 
8512 
6938 
76S0 
8832 
4941 
7Q95 
U55 
4692 


% 
+0.5 
+  1-3 
-3-8 
+0.9 
+0.3 
+0.1 
-3-5 
+2.7 


1.8956       +2.0 
1. 6128       —2.0 


0.3592  ,     -2.9 


% 
+  21 
+  17 
+  7 
+  14 
+  4-9 
+  8.4 
+  6.2 
+37-0 

+36 
+  11.6 

+  9-3 


Basal 

H 

Calories 

Age. 

O 

n 

0 

per 
Sq.  M. 

£ 

K 

Surface 
per  Hour. 

Years. 

Kg. 

Cm. 

36 

24.2 

110.3 

33-o 

21 

64.0 

164.3 

41.2 

22 

64.1 

178.0 

40.9 

32 

74.0 

179.2 

39-8 

17 

45-2 

171.8 

36-7 

21 

63.0 

184.2 

37-4 

12 

32-7 

I4I-S 

43 

63.8 

48 

93-0 

149.7 

37-9 

26 

57-6 

164.8 

33-S 

2 

6-3 

73-2 

Remarks. 


A  cretin. 

Normal. 

Normal. 

Normal. 

Diabetes. 

Normal. 


Wry  fat. 

Normal. 


As  the  "Linear  Formula"  involved  taking  19  measure- 
ments, a  simpler  procedure  was  sought.  The  formula  A  = 
W3  XH!X  167.2,  in  which  A  =  area  in  square  meters,  W  = 
weight  in  kilograms,  and  H  =  height  in  centimeters,  was  found 
to  give  an  average  error  of  2.2  per  cent.  The  average  error 
could  be  reduced  to  1-.7  per  cent,  by  using  the  formula, 

A  =  W0-425  X  H°-72S  X  71.84 

Based  on  this  formula  a  chart1  has  been  devised  by  which  it  is 
possible  to  estimate  the  surface  area  at  a  glance.  It  is  re- 
produced in  Fig,  9. 

The  old  formula  of  Meeh  gives  a  close  approximation  to 
34.7  calories  per  square  meter  of  surface  per  hour  as  the  meas- 


863. 


1  Du  Bois,  D.  and  E.  F.:  "Archives  of  Internal  Medicine,"  1916,  xvii, 


126 


SCIENCE    OF    NUTRITION 


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THE  REGULATION  OF  TEMPERATURE         1 27 

ure  of  the  basal  metabolism.  In  people  of  normal  shape 
this  result  is  so  constant  that  it  justifies  the  conclusion  that 
the  basal  heat  production  can  be  determined  by  Meeh's  for- 
mula, whether  Meeh's  formula  for  determining  surface  area  is 
correct  or  not. 

The  new  formula  gives  the  following  results,  the  subjects 
being  men  between  the  ages  of  twenty  and  fifty  years : 

Average  Maximum 

Calories  Variation  from 
per  Sq.  Meter  Average 

per  Hour.  in  Per  Cent. 

Average    9  normal  controls  (Du  Bois1) 39.7  +4  and  —6 

Average    9  normal  controls  (Means2) 39.6  +  7-6  and  —7.1 

Average  82  normal  controls  (Benedict3) 38.9  usually  ±  10 

As  the  results  of  Du  Bois  were  obtained  with  calorimeter 
experiments  of  two  or  three  hours'  duration,  the  figure  39.7 
calories  per  square  meter  of  body  surface  per  hour  may  be 
accepted  as  closely  approximating  the  normal  basal  heat 
production  of  adult  men.  The  experiments  of  Means  and  of 
Benedict  were  accomplished  with  the  Benedict  unit  apparatus 
and  bring  confirmatory  evidence. 

Boothby4  finds  that  the  metabolisms  of  23  patients  who 
recovered  their  health  after  operations,  and  who  had  been 
confined  in  the  hospital  between  twenty  and  fifty  days,  most 
of  the  time  in  bed,  were  within  ±  10  per  cent,  of  the 
Du  Bois  normal  standard.  This  establishes  the  validity  of 
the  use  of  this  measure  of  the  basal  metabolism  as  a  criterion 
of  an  altered  metabolism  in  hospital  patients. 

Du  Bois5  presents  the  following  standards  of  basal  metab- 
olism with  regard  to  age  and  sex.  Figure  10  gives  a  graphic 
presentation  of  the  data  as  applied  to  men. 

1  Gephart  and  Du  Bois:    "Archives  of  Internal  Medicine,"  1916,  xvii,  902. 

2  Means:  "Journal  of  Medical  Research,"  1915,  xxxii,  121;  "Journal  of 
Biological  Chemistry,"  1915,  xxi,  263. 

3  Benedict,  Emmes,  Roth,  and  Smith:  "Journal  of  Biological  Chemistry," 
1914,  xviii,  139. 

*  Boothby:  Oral  communication,  published  by  permission. 
5  Du  Bois:   "Archives  of  Internal  Medicine,"  1916,  xvii.  887,  and  Aub  and 
Du  Bois,  unpublished. 


128 


SCIENCE    OF    NUTRITION 


THE  REGULATION  OF  TEMPERATURE 


129 


Subjects. 

Age  in  Years. 

Calories  per  Hour  per  Square  Meter. 

Meeh. 

Du  Bois 
(Height-Weight). 

Boys 

12-13 
20-50 
20-50 
50-60 
50-60 
77-83 

45-7 
34-7 
32-3 
30.8 

28.7 

49-9 
39-7 
36.9 
35-2 

32-7 
35-i 

Men 

Women 

Men 

Women 

Men 

The  table  shows  that  boys  just  before  puberty  have  a  high 
metabolism  (see  p.  559),  that  men  have  a  higher  metabolism 
than  women,  and  that  with  advancing  age  there  is  no  longer 
the  same  intensity  of  oxidation  as  in  the  prime  of  life. 

The  greater  validity  of  the  Du  Bois  formula  over  that  of 
Meeh  is  shown  in  the  following  comparison  by  Du  Bois  of 
the  metabolism  of  fat  and  thin  subjects,  computed  in  larger 
part  from  the  work  of  Benedict,  Emmes,  Roth,  and  Smith: 


Number  of 
Subjects.  " 

Calories  per  Sq.  Meter  Aver- 
age Variation  from  Normal 
Standard  in  Per  Cent. 

Calories  per 
Kilogram  in 
Twenty-four 

Meeh. 

Du  Bois. 

Hours. 

Fat  men 

5 
4 
7 
6 

-7.6 

+  6.4 

—  12.2 

+  4-2 

-4.0 

-5-o 

0. 

-4.0 

21.9 
29.0 
19.4 

29.1 

Thin  men 

Fat  women 

Thin  women 

It  is  evident  from  this  analysis  that  although  thin  women 
produce  about  50  per  cent,  more  heat  per  kilogram  of  body 
substance  than  their  obese  companions,  yet  per  square  meter 
of  surface  there  is  little  difference. 

The  metabolism  of  a  fat  boy  and  his  thin  brother  follow  the 
same  rule  (see  p.  257).  Tangl1  obtained  the  following  results 
with  pigs: 


Weight 

in  Kg. 

121.  . 

49- • 


Calories  in  Twenty-four  Hours: 
Per  Kg.  Per  Sq.  Meter  (Meeh). 

19.6  1060 

27.2  1100 


1  Tangl:   Biochemische  Zeitschrift,"  1912,  xliv,  252. 


i3° 


SCIENCE   OF    NUTRITION 


For  the  study  of  metabolism  processes  it  is  certainly 
most  fortunate  that  the  unit  of  surface  area  eliminates  the 
same  amount  of  heat  in  the  normal  adult  within  10  per  cent, 
of  a  determined  average.  The  reason  is  not  clear.  But  the 
reasons  why  the  body  temperature  is  constant  or  why  the 
menstrual  period  is  exactly  timed  are  also  not  clear,  though 
as  facts  they  are  established. 

Recent  experiments  by  Moulton1  show  that  the  nitrogen 
content  of  cattle  is  almost  exactly  proportional  to  the  surface 
area  of  the  animal.  If  the  nitrogen  content  be  a  measure  of 
protoplasmic  tissue,  these  experiments  afford  a  striking  con- 
firmation of  the  doctrine  of  Voit  that  the  heat  production  is 
proportional  to  the  mass  of  living  cells  (see  p.  45). 

However,  the  remarkable  experiments  of  Grafe  and 
Graham2  appear  to  indicate  that  notwithstanding  a  large 
addition  of  protein  to  the  organism  of  a  dog  following  fasting, 
there  is  no  increase  in  the  fundamental  metabolism.  These 
experiments  are  summarized  below: 


Date. 

Weight 
in  Kg. 

±  N  to 
Body. 

Cal- 
ories 
in  Diet. 

Calories  of 
Metabolism. 

Hours 
After 

Total. 

Per 
Sq.  M. 

Last 
Food. 

X,  25 
XI,  14 
XI,  18 

XI,   2  2 

XI,  28 
XII,  31 

Last  day  of  food. 
21st  fasting  day. 

3d  day  of  food. 

7th  day  of  food. 
13th  day  of  food. 
46th  day  of  food. 

20.15 
15.00 
18.50 
20.00 
20.05 
20.25 

-83.5 
-48.6 

+4-7 

+  79-7 

+  265.8 

2244 
2244 
2580 
1660 

1056 
672 
816 

1081 

973 
1112 

1326 
1028 
1036 

1364 
1227 
1396 

12 

12 
10 
36 
36 

After  seven  days  of  food  the  animal  recovered  all  the  weight 
and  nitrogen  lost  during  twenty-one  days  of  fasting  and  its 
heat  production  was  as  before  the  fast.     (See  also  p.  211.) 

The  organism,  therefore,  preserves  the  tropical  temperature 
of  its  cells  at  the  expense  of  a  metabolism  which  is  pro- 
portional to  the  skin  area  of  the  individual. 

1  Moulton:    "Journal  of  Biological  Chemistry,"  1016,  xxiv,  299. 

2  Grafe  and  Graham:  "Zeitschrift  fur  physiologische  Chemie,"  1911, 
lxxiii,  1. 


THE  REGULATION  OF  TEMPERATURE         131 

The  loss  of  heat  by  an  organism  at  rest  follows  these  paths: 

1.  Conduction  and  radiation. 

2.  Evaporation  of  water  from  lungs  and  skin. 

3.  Warming  the  food  ingested. 

4.  Warming  the  inspired  air  (conduction). 

The  great  outlets  for  heat  loss  are  by  conduction  and  radia- 
tion (of  which  in  the  dog  97.3  per  cent,  takes  place  through  the 
skin  and  2.7  per  cent,  through  the  lungs1)  and  through  the 
evaporation  of  water.  The  losses  through  warming  the  food, 
and  through  heat  of  the  urine  and  of  solution  of  urinary  con- 
stituents through  the  feces,  and  the  warming  of  expired  carbon 
dioxid  may  be  ordinarily  disregarded. 

The  pathway  for  the  loss  of  heat  varies  with  the  temper- 
ature of  the  environment.  At  a  low  temperature  there  is 
little  evaporation  of  water,  and  at  a  temperature  of  370  C.  there 
can  be  no  heat  loss  by  radiation  and  conduction  (except  by  a 
rise  in  body  temperature),  and  water  evaporation  removes  the 
whole  of  it.  In  the  dog  at  a  high  temperature  there  is  spread- 
ing out  of  the  limbs  to  promote  heat  loss  by  radiation  and 
conduction,  and  rapid  breathing  (polypnea)  with  extension  of 
the  hyperemic  tongue  to  promote  evaporation  of  water.  In 
the  horse  and  in  man  there  is  especially  an  outbreak  of  sweat 
which  is  not  possible  in  the  dog,  as  its  skin  does  not  secrete 
sweat. 

Du  Bois2  finds  that  the  average  loss  of  water  from  the 
lungs  and  skin  is  680  grams  per  day  in  the  normal  resting 
man  at  an  environmental  temperature  of  230  C.  and  medium 
humidity.  The  evaporation  of  this  amount  of  water  repre- 
sents an  absorption  of  heat  equal  to  24  per  cent,  of  the  total 
heat  loss.  This  latter  figure  is  in  exact  agreement  with  an 
average  of  results  previously  reported  by  Benedict  and  Car- 
penter.3    According  to  Loewy4  the  loss  of  water  of  perspira- 

1  Rubner:    "  Energiegesetze,"  1902,  p.  187. 

2  Gephart  and  Du  Bois:    "Archives  of  Internal  Medicine,"  1916,  xvii,  902. 

3  Benedict,  F.  G.,  and  Carpenter:  Carnegie  Institution  of  Washington, 
Publication  126.  1910. 

4  Loewy:   "Biochemische  Zeitschrift,"  1914,  Lxvii,  243. 


132  SCIENCE   OF    NUTRITION 

tion  per  square  meter  of  body  surface  is  greatest  in  the  arms, 
next  greatest  in  the  legs  (the  extremities  yielding  not  far  from 
75  per  cent,  of  the  total),  and  least  from  the  trunk.  The 
greatest  actual  loss  is,  however,  from  the  legs. 

Loewy  also  finds  that  in  men  without  sweat-glands  the 
evaporation  of  water  from  the  skin  may  amount  in  maximo 
to  15.6  grams  per  square  meter  per  hour,  or  800  grams  for 
the  whole  body  during  a  day.  Vasomotor  reflexes  may  play 
an  important  part  in  the  quantity  of  water  evaporated. 
Placing  the  right  forearm  in  cold  water  reduced  the  water 
elimination  from  the  right  leg  from  3.64  to  3.22  grams  per 
square  meter  of  surface  per  hour.  Washing  the  right  arm 
with  alcohol  and  ether  reduced  the  water  elimination  of  the 
right  leg  to  1.78  grams  for  the  same  unit  of  measurement.  In 
both  of  these  experiments  the  leg  showed  an  increase  above 
the  normal  evaporation  of  water  after  the  removal  of  the 
stimulus  of  cold  from  the  arm. 

Generally  speaking,  there  is  little  difference  between  the 
temperature  of  the  inner  organs  of  the  body.  Heidenhain,1 
confirming  earlier  work  of  Claude  Bernard,  found  that  in 
84  out  of  94  experiments  with  dogs  the  temperature  of  the 
right  ventricle  was  higher  than  that  of  the  left,  two-thirds 
of  the  cases  showing  differences  between  o.i°  to  0.30.  Claude 
Bernard2  states  that  during  digestion  the  blood  of  the  hepatic 
vein  is  o.i°  higher  than  that  of  the  portal  vein.  Quincke3 
found  that  the  temperature  of  the  empty  stomach  of  a  boy 
was  constantly  0.120  higher  than  the  rectal  temperature,  and 
that  after  the  ingestion  of  500  c.c.  of  water  at  a  temperature 
of  200  C.  the  original  temperature  was  not  regained  for  seventy 
to  seventy-five  minutes.  Rancken  and  Tigerstedt4  find  a  tem- 
perature in  the  stomach  of  a  boy  with  a  gastric  fistula  which 
averages  0.090  higher  and  is  in  maximo  0.20  higher  than  that 
of  the  rectum. 

1  Heidenhain:    "Pfliiger's  Archiv,"  1871,  iv,  558. 

2  Bernard:   "Lecons  de  physiologie  operatoire,"  Paris,  1879,  p.  481. 

3  Quincke:    "Archiv  fur  exp.  Path,  und  Pharm.,"  1889,  xxv,  375. 

4  Rancken  and  Tigerstedt:   "Skan.  Archiv  fur  Physiologie,"  1909,  xxi,  85. 


THE  REGULATION  OF  TEMPERATURE         1 33 

Regarding  the  surface  temperature,  Henriques  and  Hansen1 
report  the  following  temperatures  at  different  depths  in  the  fat 
of  the  hog's  back  just  one  side  of  the  median  line: 

c. 

1  cm.  under  the  skin 33  7° 

2  "         "  " 34-8° 

3  ;;    ;;       ;; 37-0° 

4         ,  39-°° 

Rectal  temperature 39-9° 


The  environmental  temperature  was,  unfortunately,  not  noted. 
It  must  be  evident  that  under  these  conditions  blood  coming 
from  the  internal  organs  must  lose  heat  to  the  cooler  surface 
of  the  organism. 

Benedict  and  Slack2  studied  the  simultaneous  records  of 
rectum,  vagina,  axilla,  breast,  groin,  hand,  arm,  and  mouth, 
and  concluded  that  aside  from  the  skin  temperature  a  rise  or 
fall  in  rectal  temperature  is  accompanied  by  a  corresponding 
rise  and  fall  in  temperature  of  all  other  parts  of  the  body  in 
man. 

Coleman  and  Du  Bois3  find  that  in  fever,  under  conditions 
of  a  changing  blood-supply  to  the  skin,  well-covered  surface 
thermometers  give  a  more  accurate  indication  of  the  average 
change  in  body  temperature  than  does  the  rectal  thermometer. 
As  the  measurement  of  the  amount  of  heat  gained  or  lost  by  an 
organism  during  an  experiment  in  which  direct  calorimetry 
is  determined  is  effected  through  the  observation  of  the  changes 
of  body  temperature,  this  is  an  important  matter.  It  may  be 
stated  as  a  general  principle  that  when  there  is  a  wide  varia- 
tion in  rectal  temperature  direct  and  indirect  calorimetry  do 
not  usually  agree  as  closely  as  when  there  is  little  alteration 
in  body  temperature,  which  indicates  that  the  blood  is  not 
at  all  times  so  distributed  throughout  the  body  that  the  aver- 
age rise  throughout  all  the  parts  is  equal  to  the  rise  in  the  rec- 

1  Henriques  and  Hansen:   "Skan.  Archiv  fur  Physiologie,"  1901,  xi,  161. 

2  Benedict  and  Slack:   Carnegie  Institution  of  Washington,  Publication 

155,  19"- 

3  Coleman  and  Du  Bois:   "Archives  of  Internal  Medicine,"  19 15,  xv,  887. 


134  SCIENCE   OF   NUTRITION 

turn  alone.  Yet,  on  the  whole,  the  rectal  temperature  is  the 
best  guide  available. 

Some  idea  of  the  activity  of  the  blood  flow  which  equalizes 
the  body  temperature  may  be  obtained  from  the  observations 
of  Burton-Opitz,1  from  which  may  be  calculated  that  an  amount 
of  blood  equal  to  the  entire  amount  in  the  body  of  a  dog 
traverses  the  liver  every  three  minutes. 

'  It  has  been  seen  that  Lavoisier  noticed  that  cold  increases 
the  metabolism.  This  has  been  abundantly  confirmed.  The 
simplest  illustration  of  this  action  is  to  be  found  in  fasting 
animals.  Rubner  has  called  this  increase  of  metabolism  and, 
therefore,  of  heat  production  the  chemical  regulation  of  the 
body  temperature  (see  p.  1 1 8) .  It  is  the  same  as  burning  more 
coal  in  the  furnace  on  a  cold  day  in  order  to  maintain  the  tem- 
perature of  the  house.  Voit  had  previously  demonstrated 
this  action  in  the  case  of  a  man  (see  below). 

It  has  been  noted  that  a  constant  basic  quantity  of  energy 
is  necessary  to  maintain  the  life-processes  of  a  warm-blooded 
animal  situated  in  a  tropical  environment.  In  this  case  the 
energy  of  metabolism  is  directly  concerned  in  maintaining  the 
vibrant  motions  of  the  molecules  of  protoplasm  (see  p.  301) 
and  heat  production  is  a  secondary  result.  If,  now,  the  organ- 
ism be  subjected  to  the  influence  of  a  cold  environment,  there 
is  an  increased  production  of  heat  which  is  directly  derived  from 
metabolized  substances  and  the  mission  of  which  is  to  maintain 
the  temperature  of  the  body  at  the  tropical  point.  It  will 
also  be  shown  in  another  place  how  this  passive  increase  in 
heat  production  through  "chemical  regulation,"  which  is 
induced  without  visible  motion  on  the  part  of  the  animal,  may 
become  unnecessary  if  instead  the  needed  heat  be  obtained 
from  other  sources,  as  from  the  increased  heat  production 
incident  to  muscular  work  or  to  food  ingestion. 

Rubner  placed  a  fasting  guinea-pig  in  a  bell-jar  which  was 
ventilated  so  that  the  carbon  dioxid  production  could  be 

'Burton-Opitz:  "Quarterly  Journal  of  Experimental  Physiology,"  1912, 
v,  189. 


THE    REGULATION   OF   TEMPERATURE 


135 


determined.     The  temperature  of  the  bell-jar  could  be  changed 
by  immersing  it  in  water.     The  following  were  the  results: 

ACTION  OF   CHEMICAL   REGULATION   IN  THE  GUINEA-PIG 


Temperature  of  Air. 


0.0 
11.10 
20.80 
25-7° 
30-3° 
34-9° 
40.00 


Temperature  of 
Animal. 


Grams  of  CO2  in 

One  Hour  per  Kg. 

Animal. 


2.905 

2. 151 
I.766 
I.54O 
I-3I7 

1-273 
1-454 


Percentage 

Change  of  CO2  for 

Each  i°  C.  Rise  in 

Temperature  of 

Air. 


—  2.67 

—  0.71 
+  2.82 


It  is  evident  from  the  table  that  there  was  a  constant  de- 
crease in  the  metabolism  as  the  air  was  warmed  from  o°  to  350 
C.  The  metabolism  at  o°  was  two  and  a  half  times  that  at  300, 
an  increase  as  pronounced  as  is  incurred  as  the  result  of  severe 
muscular  work.  The  animal  at  o°  was  not  observed  to  move 
around  any  more  than  he  did  at  300.  These  results  have  been 
confirmed  by  Murschhauser.1  Other  experiments  confirmed 
Rubner  in  the  view  that  the  critical  temperature,  or  the  tem- 
perature of  the  minimum  metabolism,  lay  at  330.  At  this 
point  temperature  had  the  least  influence  on  total  metabolism. 
When  the  temperature  is  raised  from  300  there  is  at  first  no 
increase  in  the  metabolism.  This  is  due  to  the  action  of  the 
apparatus  for  the  physical  regulation  of  body  temperature. 
As  the  temperature  rises  the  blood-vessels  of  the  skin  become 
dilated  and  the  evaporation  of  water  from  the  body  is  pro- 
moted. These  factors  tend  to  maintain  the  normal  tempera- 
ture of  the  organism  by  physical  means.  If  the  temperature 
of  the  air  be  high,  so  that  the  physical  regulation  be  not 
sufficient  to  cool  the  body,  then  a  supernormal  temperature 
ensues.  Such  a  febrile  temperature  raises  the  metabolism 
by  warming  the  cells,  as  is  seen  in  the  table  of  the  experiment 
in  which  the  guinea-pig  was  exposed  to  a  temperature  of 
400.     The  range  of  the  physical  regulation — that  is,  the  period 

1  Murschhauser:   "Zeitschrift  fiir  physiologische  Chemie,"  1912,  lxxix,  301. 


136 


SCIENCE   OF   NUTRITION 


during  which  external  temperature  change  does  not  alter 
metabolism — depends,  according  to  Rubner,  on  the  natural 
protections  which  an  animal  possesses  which  insure  him 
against  heat  loss.  These  are  two  in  number — the  hairy 
covering  and  the  thickness  of  the  layer  of  subcutaneous 
fat. 

Rubner  has  shown  that  the  hair  of  the  black  cat,  black 
lamb,  rabbit,  skunk,  raccoon,  mink,  musk-deer,  and  sheep  is  of 
itself  relatively  light  in  weight,  but  that  the  fur  contains  a 
very  large  quantity  of  air.  The  whole  of  the  fur  covering  of 
these  animals  consists  of  between  97.3  and  98.8  per  cent,  of 
air.  The  fur,  therefore,  really  consists  of  air  with  between  1.2 
and  2.7  per  cent,  of  hair.  The  slight  conductivity  of  the  fur 
is  principally  dependent  on  this  layer  of  stationary  air.  If  an 
animal  be  covered  with  a  fur  containing  this  stagnant  air,  he 
will  be  better  protected  from  loss  of  heat  than  if  he  had  none, 
and  also  less  susceptible  to  the  influence  of  cold  upon  the  sur- 
face of  his  skin.  This  protective  covering  therefore  extends 
the  range  of  the  physical  regulation. 

Rubner1  gives  the  following  experiment  showing  the  in- 
fluence of  temperature  on  a  small  fasting  dog  with  long 
hair: 

ACTION  OF  CHEMICAL  REGULATION  IN  THE  DOG 


1st. 
2d. 
3d. 
4th 
5th 


1.80 
1.56 
1.52 
1.56 
1.42 


0.06 
0.06 
0.06 
0.06 
0.06 


1.62 
1.58 
1.62 


Pi  -i 

O  H 


20.0 
22.4 
28.2 
l8.9 

17-3 


1.1 

1.0 
1.0 
1.0 

0.9 


21.0 
23-4 
29.1 
19.9 


14.9 
18.0 
23-9 
14-5 
13-7 


u 


46.5 
40.4 

39-5 
4°-5 
37-0 


183.6 
224.6 
294.7 
179.0 
169.3 


230.1 
264.6 
334-2 
219-5 
206.3 


20.0 
i5-2c 
7-6c 
3o.oc 

25. 2C 


One  observation  was  made  in  this  experiment  on  the  dog 
which  was  not  possible  in  the  case  of  the  guinea-pig,  and  that 
1  Rubner:   "Die  Gesetze  des  Energieverbrauchs,"  1902,  p.  105. 


THE  REGULATION  OF  TEMPERATURE         137 

concerned  the  nitrogen  excretion.  The  nitrogen  excretion  for 
twenty-four  hours  is  not  increased  by  exposing  the  dog  to  a 
temperature  of  7. 6°.  The  increased  metabolism  is  entirely 
at  the  expense  of  fat.  We  have  seen  that  this  may  also  be 
true  of  work  which  may  be  accomplished  at  the  expense  of 
fat  without  raising  the  protein  metabolism. 

Reduced  to  terms  of  calories  produced  per  kilogram  of 
dog,  the  following  results  are  obtained: 

Temperature.  Calories  per  Kilo. 

7.60 86.4 

15-°° 63-° 

20.00 55.9 

25-0° 54-2 

30.00 56.2 

35-0° 68.5 

A  temperature  of  200  was  readily  borne  by  this  dog  with- 
out any  increase  of  his  metabolism.  The  period  of  unchang- 
ing metabolism  extended  over  at  least  ten  degrees  between 
200  and  300,  during  which  time  the  physical  regulation  alone 
sufficed  to  maintain  evenly  the  body's  temperature.  At 
350  a  decided  increase  of  heat  production  set  in,  on  account  of 
the  warming  of  the  cells  through  insufficient  heat  loss.  That 
the  range  of  the  physical  regulation  of  the  temperature  of  this 
small  dog  was  due  to  his  long  hair  is  shown  by  the  change  in 
his  metabolism  after  shaving  him.  Rubner  shows  this  in  the 
following  table: 


Temperature. 


20 

25 
3° 


It  is  clearly  seen  that  this  dog  lost  his  power  of  physical 
regulation  between  200  and  300  as  soon  as  he  lost  his  covering 
of  hair.     His  metabolism  became  like  that  of  the  guinea-pig, 


138  SCIENCE    OF   NUTRITION 

increasing  with  a  reduction  of  temperature  from  300  downward, 
an  illustration  of  chemical  regulation. 

E.  Voit1  shows  that  the  metabolism  of  a  pigeon  may  be 
doubled  after  removing  its  feathers. 

Babak2  finds  that  if  rabbits  are  shaved  and  varnished  with 
starch  paste  their  metabolism  rises  140  per  cent.,  which  in- 
crease maintains  their  body  temperature  at  the  normal  for 
several  weeks,  although  the  room  temperature  be  between 
1 50  and  200. 

To  determine  the  influence  of  the  second  factor,  that  of  the 
protecting  layer  of  fat,  Rubner3  investigated  the  influence  of 
temperature  on  the  metabolism  of  a  fasting  short-haired  dog 
at  a  time  when  he  was  emaciated,  and  compared  it  with  the 
fasting  metabolism  after  the  same  dog  had  been  fattened. 
The  results  were  as  follows: 

Dog  (Thin).  Same  Dog  (Fat). 

Temperature.  Cal.  per  Kilo.    Temperature.  Cal.  per  Kilo. 

5-i° 121.3                 7.30 120.5 

14-4° 100.9               15-5° 83.0 

23.30 70.7               22.O0 67.0 

30. 6° .' 62.0             31.0° 64.5 

It  appears  from  the  above  that  the  metabolism  of  the  dog 
was  the  same  at  a  low  temperature  in  both  cases,  but  that  the 
minimum  metabolism  was  almost  reached  at  a  temperature  of 
220  when  the  dog  had  a  protective  covering  of  fat,  which  was 
not  the  case  when  he  was  thin.  The  presence  of  adipose 
tissue,  therefore,  acts  in  the  same  way  as  does  a  warm  fur  to 
extend  the  range  of  the  physical  regulation,  and  to  delay  the 
onset  of  the  chemical  regulation  of  body  temperature. 

The  physical  regulation  may  be  increased  by  certain 
voluntary  acts,  such  as  are  observed  when  a  dog  exposed  to 
cold  lies  down  and  curls  himself  up  in  such  a  way  as  to  offer 
as  small  an  exposed  surface  as  possible.  The  contrast  to  this 
is  offered  when  on  a  hot  day  the  dog  lies  on  his  back  and  extends 
his  limbs  so  as  to  promote  the  loss  of  heat. 

1  Voit:    " Sitzungsber.  der  Ges.  fiir  Morph.  u.  Physiol.,"  1904,  xix,  39. 

2  Babak:   "Pfliiger's  Archiv,"  1905,  cviii,  389. 

3  Rubner:   Loc.  cit.,  1902,  p.  137. 


THE  REGULATION  OF  TEMPERATURE         139 

Rubner1  also  cites  an  important  modification  of  metabolism 
through  a  variation  in  the  humidity  of  the  atmosphere. 

At  a  medium  temperature  during  fasting  (as  well  as  on  a 
medium  diet)  the  metabolism  of  a  dog  was  practically  un- 
affected by  an  increase  of  humidity  in  the  air,  as  appears 
below : 

Calories  in  Humidity  in 

Temperature  20. 20  24  Hours.  Per  Cent. 

Dry  day 258.4  34 

Hurnid  day 256.6  69 

More  on  dry  day 1.8 

However,  on  a  liberal  diet  the  metabolism  increases  on  a  damp 
day  even  at  a  medium  temperature,  as  for  example: 

Calories  in  Humidity  in 

Temperature  20.20  24  Hours.  Per  Cent. 

Very  dry  day 249.4  13 

Humid  day 261.9  66 

More  on  humid  day 12.5 

The  increase  is  5  per  cent. 

On  a  very  hot  day  (on  a  moderate  fat  diet)  the  dog's  met- 
abolism is  increased  by  the  presence  of  moisture  in  the 
atmosphere. 

Temperature  35  °. 
Calories  per  Kg.  Humidity  in  Per  Cent. 

69. 2S  9.1 

73-54  30-0 


Under  these  circumstances  the  metabolism  rose  6.1  per  cent, 
in  the  more  humid  air.  There  was  probably  an  overwarming 
of  the  cells  on  account  of  the  difficulty  of  heat  loss  by  evapora- 
tion of  water.  A  cold,  damp  environment  of  o°  to  50  temper- 
ature also  favors  an  increased  metabolism.  Rubner  attributes 
this  action  of  humidity  to  the  increased  conductivity  of  a  hair 
covering  containing  moisture,  and  says  that  this  loss  may  be 
partially  balanced  by  a  decreased  evaporation  of  water  from 
the  lungs. 

1  Rubner:   "Energiegesetze,"  1902,  p.  188. 


140 


SCIENCE    OF   NUTRITION 


Murschhauser  and  Hidding1  have  experimented  with 
guinea-pigs'  placed  in  various  environmental  temperatures 
and  furnished  either  with  perfectly  dry  air  or  air  completely 
saturated  with  moisture.  At  350  the  well-known  influence  of 
air  saturated  with  water  increased  the  body  temperature  and, 
therefore,  the  metabolism.  At  both  200  and  50  the  influence 
of  cold  was  accentuated  by  excessive  dryness  of  the  air,  so 
that  the  heat  production  was  about  10  per  cent,  higher  than  in 
moist  air  at  the  same  temperature.  This  is  explained  by  the 
fact  that  in  dry  air  evaporation  of  water  from  the  lungs 
increased  the  loss  of  heat  by  the  animal  which  was  compensated 
for  by  an  increased  metabolism. 

The  metabolism  and  the  manner  of  heat  loss  may,  therefore, 
be  variously  affected  by  the  condition  of  the  atmosphere  as 
regards  moisture. 

On  days  of  ordinary  dryness  Rubner2  calculates  the  follow- 
ing division  of  the  heat  loss  in  a  starving  dog  under  the  in- 
fluence of  different  temperatures: 

INFLUENCE   OF   TEMPERATURE    ON   MANNER    OF   HEAT   LOSS 


Temperature. 

Calories  Lost  by 

Conduction  and 

Radiation. 

Calories  Lost  by 
Evaporation  of 

Water. 

Total 
Calories  of 
Metabolism. 

Humidity 
in  Per  Cent. 

7° 

iS° 

20° 

25° 

30° 

78.5 
55-3 
45-3 
41.0 

33-2 

7-9 

7-7 

10.6 

13-2 

23.0 

86.4 
63.0 
55-9 
54-2 
56.2 

24 
34 
29 
19 
14 

It  is  clear  that  at  70  only  a  little  heat  is  lost  by  the  evaporation 
of  water  and  the  greater  part  by  conduction  and  radiation. 
As  the  surrounding  air  becomes  warmer  the  power  to  lose  heat 
by  radiation  and  conduction  diminishes,  and  the  loss  through 
the  evaporation  of  water  increases. 

Rubner  has  charted  this  experiment  after  making  allow- 
ances3 for  the  varying  moisture  conditions.     The  chart  is 

1  Murschhauser  and  Hidding:   "  Biochemische  Zeitschrift,"  1912,  xlii,  357. 

2  Rubner:    "Energiegesetze,"  1902,  p.  193. 

3  Rubner:   "Archiv  fur  Hygiene,"  1891,  xi,  208. 


THE  REGULATION  OF  TEMPERATURE 


141 


reproduced  in  Fig.  1 1 ,  and  epitomizes  the  method  of  heat  loss 
in  a  starving  dog  under  the  influence  of  varying  temperatures. 
The  discussion  of  the  metabolism  has  given  a  foundation 
for  the  understanding  of  the  basic  requirement  of  an  organism. 
The  minimum  requirement  for  energy  is  seen  to  be  present 


?\o      so  Cabries 

Fig.  11. — Rubner's  chart  showing  the  manner  of  heat  loss  at  different  room 
temperatures  in  the  dog.  Blue,  Heat  loss  in  calories  through  evaporation  of 
water.     Red,  Heat  loss  in  calories  through  radiation  and  conduction. 

The  distance  between  opposite  points  of  the  curved  line  represents  the  total 
metabolism  at  a  particular  temperature. 


when  the  fasting  organism  is  surrounded  by  an  atmosphere 
having  a  temperature  of  300  to  350.  This  may  be  called  the 
basal  metabolism,  the  minimum  of  energy  compatible  with 
cell  life.  This  basal  metabolism  is  modified  by  temperature, 
by  food,  and  by  work,  and  it  is  an  important  factor  to  keep  in 
mind  (see  p.  124). 


142  SCIENCE   OF   NUTRITION 

The  principles  laid  down  here  regarding  the  lower  animals 
apply  equally  to  man.  He  too  may  come  under  the  influence 
of  chemical  regulation,  although  he  constantly  endeavors  to 
maintain  the  surface  of  his  skin  at  a  tropical  temperature 
through  the  use  of  clothes.  His  heat  loss  may,  like  the  dog's, 
be  more  difficult  if  he  be  covered  with  a  thick  layer  of  fat, 
and  his  metabolism  is  also  influenced  by  atmospheric  condi- 
tions of  moisture,  wind,  and  temperature. 

One  of  the  earliest  demonstrations  of  the  action  of  chemical 
regulation  was  afforded  by  Voit,  who  placed  a  fasting  man 
weighing  70  kilograms  in  the  Pettenkofer-Voit  respiration 
apparatus  and  determined  the  carbon  dioxid  and  nitrogen 
output  for  six  hours.  The  person  accustomed  himself  to  the 
given  temperature  by  staying  under  its  influence  for  some 
time  previous  to  the  commencement  of  the  experiment.  In 
the  cold  experiments  the  ventilating  air  was  derived  from  the 
winter  atmosphere.  For  the  warm  periods  the  air  was 
artificially  heated.  The  subject  of  the  experiment  wore 
clothing  which  was  comfortable  in  the  usual  warm  atmosphere 
of  the  laboratory.     Voit1  gives  the  following  results: 

EFFECT  OF  TEMPERATURE  ON  THE  METABOLISM  OF  A  FASTING 

MAN.     SIX-HOUR   PERIODS 

C02  Excreted      N  in  Urine 
Temperature.  in  G.  in  G. 


4.4  ° 210.7  4 

6. 50 206.0  4 

9.00 I92°  4 

14-3° x55-i  3 

16.20 158.3  4 

23.70 164-8  3 

24.20 166.5  3 

26. 70 160.0  3 

30.00 1706 


The  nitrogen  elimination  remains  unaffected  by  temper- 
ature. At  the  ordinary  room  temperature  there  scarcely 
seems  to  be  any  increase  in  carbon  dioxid  output,  but  at  the 
lower  temperatures  the  quantity  of  the  fat  metabolism  is 
markedly  increased,  as  shown  by  the  rise  of  carbon  dioxid 

1  Voit:   "Zeitschrift  fur  Biologie,"  1878,  xiv,  80. 


THE   REGULATION   OF   TEMPERATURE  143 

elimination.  The  individual  sat  quietly  in  a  chair,  but  at 
a  temperature  of  4.40  C.  could  not  prevent  himself  from 
shivering. 

The  whole  effect  of  the  chemical  regulation  in  man  has  been 
attributed  by  Johansson1  and  also  by  Sjostrom2  to  the  ad- 
ditional metabolism  due  to  shivering.  Voit  did  not  believe 
that  this  could  be  the  cause,  nor  that  the  increased  respiratory 
activity  could  account  for  the  rise  in  metabolism.  Voit 
believed  the  increase  to  be  a  reflex  stimulus  of  cold  on  the  skin 
which  raised  the  power  of  the  muscle  cells  to  metabolize. 
Voit's  views  have  been  confirmed  in  Rubner's  laboratory3 
in  the  following  series  of  experiments  on  a  man: 

Temperature.  CO2  in  Grams  per  Hour. 

15° 32-3 

200 30.0 

23° 27.9 

25° 31-7 

29° 32-4 

In  this  experiment  there  was  no  shivering  at  a  temperature 
of  1 50,  and  yet  the  metabolism  increased  from  what  it  was  at 

It  has  also  been  shown  that  cool  baths  and  winds  increase 
the  metabolism,  which  must  be  effected  through  the  chemical 
regulation.  Lefevre4  states  that  a  man  who  has  been  inured 
to  it  may  sit  naked  for  several  hours  in  a  cold  wind  without 
a  reduction  of  body  temperature. 

Rubner5  has  measured  the  effect  of  baths  and  douches 
lasting  three  and  a  half  to  five  minutes.  When  the  water  has 
a  temperature  of  i6°  he  finds  that  the  carbon  dioxid  elimina- 
tion may^be  very  largely  increased,  especially  in  the  case  of  the 
douche.  The  effect  of  the  douche  was  more  marked  if  taken 
before  breakfast  when  the  intestinal  tract  was  free  from  food. 
The  results  before  breakfast  were  as  follows: 

Johansson:    "Skan.  Archiv  fur  Physiologie,"  1897,  vii,  123. 
2  Sjostrom:   "Skan.  Archiv  fur  Physiologie,"  1913,  xxx,  1. 


3  Rubner 

4  Lefevre 
6  Rubner 


"Energiegesetze,"  1902,  p.  203. 
"Comptes  rendus,"  1894,  p.  604. 
"Archiv  fur  Hygiene,"  1903,  xlvi,  390. 


144  SCIENCE    OF   NUTRITION 

INFLUENCE   OF   COLD   BATHS   ON  METABOLISM   IN  MAN 


Volume  of  respiration. . 
Carbon  dioxid  excreted. 
Oxygen  absorbed 


Douche  i6°.     In- 
crease in  Per 
Cent. 


54-5 
149-5 

IIO.I 


Bath  i6°.     In- 
crease in  Per 
Cent. 


22.9 
64.8 
46.8 


A  cold  bath,  especially  a  douche,  will  therefore  stimulate 
to  a  greatly  increased  metabolism.  The  mechanical  stimulus 
of  the  falling  cold  water  apparently  acts  reflexly  to  increase  the 
metabolism  greatly,  as  it  certainly  does  the  magnitude  of  the 
respiration.  The  respiratory  quotient  indicates  that  the  in- 
creased metabolism  is  at  the  expense  of  the  glycogen  supply. 
There  is  an  after-effect  which  lasts  about  one  and  a  half  hours, 
indicating  an  increased  metabolism  during  that  time.  This 
may  be  the  expression  of  the  body's  attempt  to  maintain  a 
normal  temperature  after  being  somewhat  cooled  (see  also  p. 
322). 

It  is  obvious  that  a  cold  bath  will  be  likely  to  induce  shiver- 
ing unless  by  mechanical  effort,  such  as  swimming,  the  metabo- 
lism is  increased  so  as  to  supply  calorific  energy  in  another 
way  than  through  chemical  regulation  (see  p.  312). 

A  bath  of  350  has  no  effect  on  metabolism. 

Rubner  finds  that  a  bath  at  440  again  increases  the  metab- 
olism, the  increase  being,  for  the  volume  of  respiration,  18.8 
per  cent.,  for  carbon  dioxid  32.1  per  cent.,  and  for  oxygen  17.3 
per  cent.  This  is  probably  due  to  the  overwarming  of  the 
cells.  Baths  at  this  temperature  find  favor  among  the 
Japanese. 

Lusk1  found  that  immersion  before  breakfast  of  men 
in  baths  at  a  temperature  of  8°  which  contained  cracked  ice 
increased  the  heat  production  during  a  subsequent  period  of 
violent  shivering  to  180  per  cent,  above  the  normal.  The 
metabolism  was  the  equivalent  of  4500  calories  per  day  for  a 

1  Lusk:   "American  Journal  of  Physiology,"  1010-11,  xxvii,  427. 


THE  REGULATION  OF  TEMPERATURE         1 45 

man  weighing  64.7  kilograms.  From  the  respiratory  quo- 
tient of  0.85  which  was  found,  it  may  be  computed  that  ap- 
proximately half  of  this  energy  was  derived  from  carbohy- 
drates and  half  from  fat.  It  is  known  that  cold  tends  to  remove 
glycogen  from  the  animal  body  (see  p.  458),  and  it  has  been 
shown  by  Freund  and  Marchand1  that  a  low  environmental 
temperature  increases  the  amount  of  sugar  in  the  blood. 

Schapals2  brings  confirmatory  evidence  as  to  the  outcome 
of  immersion  of  men  in  hot  and  cold  baths: 

0>  per  Increase  in  02 

Minute.  R.  Q.  in  Per  Cent. 

Normal 223.7  °-78 

Hot  bath  at  42  ° 274.0  1.09  15 

Normal 278.7  0.78 

Cold  bath  at  17  ° 601.0  0.86  116 

The  higher  respiratory  quotients  obtained  may  in  part  be 
due  to  a  quickened  respiration  and  consequent  elimination 
from  the  blood  of  carbon  dioxid  not  belonging  to  the  metab- 
olism of  the  period  The  German  term  "Auspumpung" 
properly  defines  this  procedure.  In  metabolism  work  this 
possibility  should  be  always  sharply  borne  in  mind. 

The  effect  of  wind  is  such  that  an  imperceptible  air  current 
may  have  a  very  pronounced  influence.  Rubner3  has  shown 
that  wind  becomes  perceptible  when  it  attains  a  velocity  of  0.4 
to  0.5  meter  a  second,  and  that  if  a  wind  much  below  this  thresh- 
old value,  having  a  velocity  of  0.18  meter  per  second,  act  upon 
the  exposed  area  of  the  arm,  there  is  an  increased  heat  loss 
of  between  19  and  75  per  cent.,  depending  on  the  temperature 
of  the  wind,  above  what  would  be  lost  were  the  air  quiet. 

The  effect  of  wind  of  moderate  humidity  and  different 
temperatures  on  the  metabolism  of  a  man  clad  in  summer 
clothes,  as  compared  with  the  metabolism  during  atmospheric 
calm,  is  shown  in  Wolpert's4  experiment  below: 

freund  and  Marchand:  "Archiv  fur  exp.  Path,  und  Pharm.,"  1913, 
lxxiii,  276. 

2  Schapals:    "Zeitschrift  fur  exp.  Path,  und  Ther.,"  1912,  x,  222. 

3  Rubner:    "Archiv  fiir  Hygiene,"  1904,  1,  296. 
4Wolpert:    "Ibid.,  1898,  xxxiii,  206. 


146  SCIENCE    OF   NUTRITION 

INFLUENCE   OF  WIND   ON   METABOLISM   IN   MAN 


Temperature. 

C<U.M. 

Wind  i  Meter 
per  Second. 

Wind  8  Meters 
per  Second. 

Grams  CO2  per 
Hour. 

Grams  CO2  per 
Hour. 

Grams  CO2  per 
Hour. 

2° 

29.8 
25-1 

24.1 
25.0 

25-3 

23-7 
21.2 

28.3 

22.2 

22.2 

30.0 
30.1 
28.O 

15— 20° 

20-25° 

2C— 20° 

24.4 

5    -*     0 

21.6 

^-40° 

22.1 

According  to  this,  a  breeze  having  a  temperature  of  150 
to  200  and  moving  at  the  rate  of  about  15  miles  per  hour 
(8  meters  per  second)  has  a  greater  effect  upon  the  metab- 
olism of  a  man  clad  in  summer  clothing  than  a  temperature 
of  20  would  have  during  perfect  atmospheric  quiet.  In  all 
the  experiments  the  smallest  amount  of  carbon  dioxid  is 
eliminated  between  300  and  400. 

The  above  experiments  were  performed  on  a  thin  man,  and 
it  will  be  noticed  that  there  was  no  rise  in  his  metabolism  at  a 
temperature  of  between  350  and  400.  Rubner  explains  this  as 
due  to  the  sufficiency  of  the  evaporation  of  perspiration  on  the 
surface  for  the  cooling  of  the  organism. 

A  fat  man,  however,  with  a  thick,  ill-conducting  layer  of 
adipose  tissue  is  not  so  immune  to  the  effect  of  high  temper- 
atures upon  his  metabolism.  This  is  especially  pronounced  in 
a  damp  climate.  Thus  Rubner1  obtains  the  following  results 
from  a  fat  man  wearing  clothes : 

1  Rubner:   "Energiegesetze,"  1902,  pp.  208,  232. 


THE  REGULATION  OF  TEMPERATURE 


147 


INFLUENCE     OF     TEMPERATURE     AND     HUMIDITY     ON    THE 
METABOLISM   OF  A  FAT  MAN 


Humidity  30  Per  Cent. 

Humidity  60  Per  Cent. 

Temperature. 

CO2  in  Grams 
per  Hour. 

H2O  Evapo- 
rated per  Hour. 

CO;  in  Grams 
per  Hour. 

H:0  evapo- 
rated per  Hour. 

20° 

33-7 
36.9* 

42.&t 

56 
134 

204 
+  14  g- 

sweat. 

30.7 
44-St 

46-7§ 

17 

28-30° 

170+ 

36-37° 

31  g- 

sweat. 
186 

+  255  g- 
sweat. 

*  Body  temperature  rose  o.i°. 
f  Body  temperature  rose  0.0°. 


X  Body  temperature  rose  0.4° 
§  Body  temperature  rose  0.9° 


The  fact  that  in  the  experiment  where  there  was  30  per 
cent,  humidity  the  metabolism  largely  increased  at  360  to  370 
without  concomitant  rise  in  body  temperature  leads  Rubner 
to  theorize  that  there  must  have  been  an  overheating  of  the 
cells  where  the  metabolism  was  progressing,  even  though  this 
might  not  have  been  determinable  by  the  clinical  thermometer. 

It  appears  that  on  a  hot,  humid  day  the  metabolism  of  a 
fat  individual  may  be  50  per  cent,  higher  than  on  a  day  of 
moderate  temperature  and  the  same  humidity.  The  whole  of 
the  body  heat  is  lost  through  the  evaporation  of  water  which  is 
here  hindered  by  the  humidity.  There  is  a  large  and  exhaust- 
ing excretion  of  sweat  which  on  account  of  the  difficulty  in 
evaporation  is  not  effective  in  cooling  the  body.  At  a  moder- 
ate temperature,  where  the  greater  part  of  the  heat  loss  is  by 
radiation  and  conduction,  the  excretion  of  water  is  not  ex- 
cessive. 

Lee1  gives  the  following  table  which  shows  the  influence  of 
varying  temperatures  and  humidities  upon  the  body  tem- 
peratures of  a  group  of  normal  men : 


Period  of 
Confine- 
ment. 

20°  C. 

50  Pe?.  Cent. 

Humtdity. 

23.9°  c. 

50  Per  Cent. 

Humidity. 

30°  C. 

80  Per  Cent. 

Humtdity. 

3o°C. 
80  Per  Cent. 
Humtdity.  with 
Fan  Movement. 

8.30  A.  M. 

3.3O  P.  M. 

37.12°  C. 
36.52°  c. 

36.83°  c. 
37.02°  c. 

36.86°  C. 
37-28°  C. 

36.98°  c. 
37-37°  C. 

1  Lee:   Proceedings  of  the  Soc.  for  Ex.  Biol,  and  Med.,  1915,  xii,  72. 


148  SCIENCE    OF   NUTRITION 

There  can  be  no  doubt  that  climatic  conditions  modify 
racial  characteristics.  The  emigrant  from  northern  Europe, 
living  upon  a  farm  in  the  hot  and  often  moist  climate  of  an 
American  summer,  must  restrict  his  layer  of  adipose  tissue  if 
he  is  to  live  comfortably.  The  same  holds  true  in  Italy.  The 
difference  between  John  Bull  and  Uncle  Sam  seems  to  be  one 
of  climatic  adaptation.  On  the  contrary,  the  Eskimo  cultivates 
a  thick,  fat  layer  to  protect  himself  from  frost.  It  is  also 
interesting  to  note  that  prostrations  from  the  heat  appear  in 
New  York  with  66  per  cent,  humidity  and  a  temperature  of 
31. 50  (2.30  p.  m.,  August  24,  1905).  Rubner1  says  that  a 
lightly  clad  thin  man,  at  a  temperature  of  300  with  humidity 
at  65  per  cent.,  bore  the  effect  so  badly  that  he  feared  to  raise 
the  temperature  to  350.  This  individual  had  readily  tolerated 
350  in  dry  air. 

The  maximum  mortality  from  "summer  troubles"  in  chil- 
dren in  New  York  coincides  with  the  first  great  wave  of  heat 
accompanied  by  humidity  which  falls  upon  the  city.  Similar 
climatic  conditions  at  later  dates  are  not  so  fatal.  It  may  be 
that  the  fatality  of  these  intestinal  affections  is  due  to  the 
inefficiency  of  the  apparatus  for  the  physical  discharge  of  heat 
in  the  infant  organism.  It  is  also  possible  that  infection  may 
be  more  readily  brought  about  under  these  conditions  (p.  344). 

Another  factor  in  the  heat  regulation  of  man  is  clothes. 
Certain  savage  races  living  in  cool  climates  do  without 
clothes,  as,  for  example,  aborigines  of  Terra  del  Fuego,  who, 
according  to  the  reports  of  travelers,  substituted  a  cover- 
ing of  oil.  In  such  races  the  process  of  "hardening"  or  the 
development  of  the  physical  regulation  must  be  carried  to  a 
maximum.  In  civilized  countries  man  endeavors  to  remove 
all  the  influence  of  chemical  regulation  by  keeping  his  skin 
covered.  Only  about  20  per  cent,  of  his  surface  is  normally 
exposed  to  the  air.  The  most  important  constituent  of  clothes 
is  the  air,  which  is  a  much  worse  conductor  of  heat  than  is  the 
fiber.     This  is  especially  true  of  furs  (p.  136).     Thickness  of 

1  Rubner:  "Energiegesetze,"  1902,  p.  232. 


THE  REGULATION  OF  TEMPERATURE 


149 


the  cloth  will  give  a  greater  layer  of  air  and  will  prevent  heat 
loss  from  the  body.  A  densely  woven  cloth  prevents  proper 
ventilation  and  does  not  absorb  moisture.  In  hot  weather  a 
porous  cloth  next  to  the  skin  which  can  absorb  moisture  and 
permit  its  ready  evaporation  is  of  high  importance.  If  a 
garment  worn  next  to  the  skin  becomes  thoroughly  wet  the 
evaporation  of  sweat  at  a  high  temperature  is  largely  pre- 
vented, to  the  great  discomfort  of  the  individual,  while  at  a 
lower  temperature  heat  loss  through  conduction  is  greatly 
facilitated,  with  a  sensation  of  chill.  Two  experiments 
cited  by  Rubner1  indicate  the  effect  of  clothes  on  metab- 
olism. An  individual  was  kept  at  a  temperature  of  between 
n°  and  120  and  wore  different  clothes  at  different  times.  His 
carbon  dioxid  and  water  excretion  were  as  follows: 


INFLUENCE  OF  CLOTHES  ON  METABOLISM  IN  MAN  AT  A  TEM- 
PERATURE  OF    11°  TO    12°. 


CO2  IN 

Grams 

pep.  Hour. 

H20in 
Grams 

per  Hour. 

Remarks. 

Summer  clothes 

28.4 

26.9 

23.6 

58 

5° 
63 

Cold,  occasional  shivering. 

Chilly  part  of  the  time. 
Comfortably  warm. 

Summer  clothes  and  winter 

overcoat 

Summer  clothes  and  fur  coat . 

When  the  man  was  comfortable  the  chemical  regulation  of 
temperature  was  eliminated. 

Rubner  remarks  that  while  the  radiant  energy  of  the  sun 
is  large  in  quantity,  he  has  been  unable  to  find  any  influence 
upon  a  man  under  ordinary  circumstances,  but  believes  that  it 
may  take  the  place  of  heat  produced  through  chemical  regu- 
lation on  cold  days.  Thus  a  person  living  in  the  high  altitude 
of  Davos,  Switzerland,  feels  much  more  comfortable  in  the 
sun  on  a  cold  day  than  he  does  in  the  shade.  However, 
Zuntz  while  living  on  the  summit  of  Monte  Rosa  found  that 
sunlight  did  not  reduce  metabolism  (p.  429). 

1  Rubner:   "Energiegesetze,"  1902,  p.  225. 


150  SCIENCE    OF   NUTRITION 

Hasselbalch1  found  that  if  the  naked  body  of  a  man  was 
strongly  exposed  to  ultra-violet  rays  the  rate  of  respiration  was 
diminished  while  the  depth  was  increased.  The  skin  was  red 
with  dilated  capillaries  and  the  blood-pressure  fell.  Lind- 
hard,  in  1910,  showed  there  is  a  yearly  periodicity  of  the  res- 
piratory rate  in  the  Arctic  region,  it  being  less  in  the  spring 
and  summer  than  in  the  winter.  The  enormous  variations 
in  the  chemical  intensity  of  the  sun's  rays  in  the  Arctic  region 
are  undoubtedly  the  cause  of  this  manifestation.  Even  in 
Copenhagen  the  same  phenomenon  has  been  observed  by 
Hasselbalch  and  Lindhard.2  The  volume  of  respiration 
increases  26  per  cent,  in  the  summer.  The  intensity  of  the 
metabolic  processes  are  not  affected.  This  accords  with  the 
fact  that  there  is  no  change  in  metabolism  through  an  alter- 
tion  of  the  respiratory  rhythm  induced  by  cutting  the  pul- 
monary branches  of  the  vagus.3 

Durig  and  Zuntz4  find  that  the  climate  of  the  seashore 
does  not  influence  the  basal  metabolism,  nor  does  travel  to  the 
Canary  Islands  in  the  tropics,5  nor  the  condition  of  sea-sick- 
ness. 

The  fundamental  heat  production  in  the  organism  is  not 
reduced  by  liberating  heat  from  electric  energy  within  the 
organism.6  Thus,  although  high  frequency  currents  equal  to 
1.8  amperes  and  176  volts  were  passed  through  the  body 
during  two  and  one-half  hours  under  conditions  such  as 
avoided  high  concentration,  and  though  heat  was  produced 
thereby  which  was  equal  to  three  to  four  times  the  energy 
requirement  of  the  time,  yet  there  was  in  fact  a  slight  increase 
in  the  oxidative  processes  of  the  subjects  attributable  to  hyper- 
thermia, sweating,  increased  pulse,  and  respiratory  activity. 

1  Hasselbalch:    "Skan.  Archiv  f.  Physiol.,"  1905,  xvii,  431. 

2  Hasselbalch  and  Lindhard:  "Skan.  Arch.  f.  Physiol.,"  ion,  xxv,  361; 
Ibid.,  1012,  xxvi,  221. 

3  Rauber  and  Voit:    " Sitzungsber.  der  baeyerischen  Akademie,"  1868. 

4  Durig  and  Zuntz:  "Biochemische  Zeitschrift,"  1012,  xxxix,  422;  Ibid., 
p.  435. 

6  For  an  interesting  discussion  of  the  offects  of  tropical  light  on  white 
men  read  C.  E.  Woodruff,  "Medical  Ethnology,"  New  York,  1015. 

6  Durig  and  Grau:    "Biochemische  Zeitschrift,"  1012-13,  xlviii,  480. 


THE  REGULATION  OF  TEMPERATURE         151 

Extraneous  heat,  therefore,  will  not  replace  the  chemical 
energy  of  the  food-stuffs  in  maintaining  the  life  processes. 

In  what  follows  it  will  be  shown  that  the  ingestion  of  food 
may  add  to  the  heat  production  of  the  organism  and  diminish 
the  necessity  of  heat  production  through  chemical  regulation 
in  cold  weather.  Also  it  may  very  uncomfortably  increase 
the  production  of  heat  and  perspiration  in  warm  weather, 
especially  if  protein  be  largely  taken  (p.  247). 

From  this  chapter  the  influence  of  climate  is  seen  to  be 
noteworthy.  It  explains  why  a  temperature  of  — 400  may  be 
comfortably  borne  in  winter,  in  the  Adirondack  Mountains,  for 
example,  if  the  air  be  dry  and  still;  why  a  much  warmer  atmos- 
phere which  is  damp  and  windy  may  "cut  to  the  bone"  with 
cold;  why  a  hot,  dry  climate  may  be  entirely  comfortable,  when 
air  at  the  same  temperature  laden  with  moisture  may  strike 
down  many  fatally  and  oppress  every  one ;  and  how  the  effect 
of  heat  may  be  modified  by  the  breezes  and  baths  at  the  sea- 
shore. It  does  not  explain  the  effect  of  the  dry  sirocco  wind 
which  blows  from  the  Desert  of  Sahara,  the  universal  depress- 
ant action  of  which  has  been  attributed  to  unknown  cosmic 
influences. 


CHAPTER  V 
THE  INFLUENCE  OF  PROTEIN  FOOD 

PART  I— NITROGEN  EQUILIBRIUM 

It  has  been  thought  that  protein  is  a  food  which  is  in  itself 
sufficient  for  all  the  requirements  of  the  body.  Pfliiger1 
was  able  to  keep  a  very  thin  dog  in  good  condition  and  doing 
active  exercise  during  a  period  of  seven  months,  the  sole  diet 
being  meat  cut  as  free  from  fat  as  possible.  Pfliiger  says  that 
the  fat  and  glycogen  content  of  the  meat  ingested  could  not 
have  yielded  sufficient  energy  to  provide  for  the  action  of  the 
heart  alone.  It  must  be  remembered,  however,  that  meat  is 
not  pure  protein,  but  is  mixed  with  salts  and  water.  The 
simplest  diet  capable  of  maintaining  the  body  in  condition  is, 
therefore,  a  mixture  of  materials  or  food-stuffs.  Such  a 
mixture  of  food-stuffs  is  called  a  food.  A  food-stuff  is  a 
material  capable  of  being  added  to  the  body's  substance,  or 
one  which  when  absorbed  into  the  blood-stream  will  prevent 
or  reduce  the  wasting  of  a  necessary  constituent  of  the  organ- 
ism. 

The  food-stuffs  are: 

Proteins  (including  albuminoids). 

Carbohydrates. 

Fats. 

Salts. 

Water. 

A   food  is   a  palatable  mixture  of  food-stuffs  which  is 

capable  of  maintaining  the  body  in  an  equilibrium  of  substance, 

or  capable  of  bringing  it  to  a  desired  condition  of  substance. 

The  ideal  food  is  a  palatable  mixture  of  food-stuffs  arranged 

1  Pfliiger:   "Pfliiger's  Archiv,"  1891,  1,  98. 
152 


THE  INFLUENCE  OF  PROTEIN  FOOD  1 53 

together  in  such  proportion  as  to  burden  the  organism  with  a 
minimum  of  labor.     These  definitions  are  Voit's.1 

When  protein  alone  is  ingested  by  a  normal  adult  it  is  very 
readily  oxidized,  and  is  only  with  the  greatest  difficulty 
deposited  so  as  to  form  new  tissue  in  the  organism. 

In  the  early  experiments  of  Bischoff  and  Voit  the  fact  is 
recorded  that  a  dog  weighing  35  kilograms  may  excrete  12 
grams  of  urea  in  twenty-four  hours,  and  the  same  dog  after 
receiving  2500  grams  of  meat  may  excrete  184  grams,  fifteen 
times  as  much. 

Voit2  has  shown  that  if  that  quantity  of  meat  be  adminis- 
tered which  corresponds  to  what  is  oxidized  in  starvation, 
nitrogen  equilibrium  will  not  be  established,  but  some  of  the 
body's  flesh  will  also  be  metabolized.  This  latter  quantity 
grows  steadily  less  if  the  amount  of  meat  ingested  be  gradually 
increased  until  finally  the  point  of  nitrogen  equilibrium  is 
reached,  at  which  the  amount  of  meat  ingested  is  equal  to 
that  destroyed  in  the  body.  To  illustrate  this  Voit  gives  the 
following  table,  the  results  of  work  done  on  a  dog: 


Grams  Meat 
Administered. 

Grams  Flesh 
Destroyed. 

Change 
ln  the  Body. 

0 

233 

-233 

0 

190 

—  190 

300 
600 

379 
665 

-79 
-65 

900 
1200 

941 
1 180 

-41 
+  20 

1500 

1446 

+54 

Nitrogen  equilibrium  was  not  reached  until  1200  grams  of  meat  were  given, 
or  about  five  times  the  amount  of  the  fasting  protein  metabolism. 

The  above  experiments  were  made  in  1858.  It  is  no  longer 
customary  to  calculate  the  protein  metabolism  in  terms  of 
flesh  destroyed,  but  in  terms  of  nitrogen.  The  old-fashioned 
term  "flesh"  meant  meat  with  a  nitrogen  content  of  3.4 
per  cent.  It  served  to  illuminate  the  significance  of  metabo- 
lism at  a  time  when  few  were  instructed  in  this  field  of  work. 

E.  Voit  and  KorkunofP  have  published  a  research  of  sim- 

1  Voit:   Hermann's  Handbuch,  "Stoffwechsel,"  1881,  pp.  330,  344. 

2  Voit:   Ibid.,  1 88 1,  p.  106. 

3  E.  Voit  and  Korkunoff:    "Zeitschrift  fur  Biologie,"  1895,  xxxii,  58. 


154  SCIENCE    OF    NUTRITION 

ilar  character.  They  fed  a  dog  with  meat  which  had  been 
treated  with  lukewarm  water  to  remove  the  extractives,  and 
which  was  then  squeezed  in  a  press.  This  process  removes 
most  of  the  nitrogen-containing  substances  other  than  protein. 
A  dog  will  readily  eat  this  washed  meat  or  "protein."  The 
idea  was  to  determine  the  minimum  quantity  of  protein  which 
it  was  possible  to  ingest  and  still  maintain  nitrogen  equilibrium. 
The  different  quantities  of  meat  tabulated  below  were  given 
continuously  for  two  or  three  days  at  a  time.  Only  the  results 
of  the  last  day  of  each  of  these  periods  are  quoted :    ♦ 

Food.  N  in  Food.      N  in  Excreta.     Difference. 

Starvation o 

ioo  gm.  meat 4.10 


140 
165 
185 

200 
230 
360 
410 
360 
Starvation 


third  day. 


5-74 
6.77 

7-59 

8.20 

10.24 

11.99 

I5-58 
13.68 


3-996 

-3-996 

5-558 

-1.458 

6.495 

-Q-755 

7.217 

-0.447 

7.804 

—  0.214 

8.726 

-0.526 

10.579 

-0-339 

12.052 

—  0.062 

14-314 

+  1.266 

13.622 

+0.058 

4.026 

—4.026 

The  figures  show  that  nitrogen  equilibrium  was  reached 
only  after  supplying  three  and  a  half  times  the  amount  of 
protein  metabolized  in  starvation.  The  authors  calculate  that 
at  this  time  of  nitrogen  equilibrium  the  dog  was  still  losing  28 
grams  of  body  fat,  and  that  not  much  more  than  50  per  cent, 
of  the  total  energy  liberated  in  the  organism  was  furnished  by 
the  protein  metabolism  of  the  time.  One  may  thus  have 
nitrogen  equilibrium  without  having  carbon  equilibrium. 

Systems  of  diet  for  fat  people  are  based  on  this  knowledge. 
A  loss  of  protein  is  highly  undesirable,  while  a  gradual  loss  of 
adipose  tissue  may  be  a  great  relief  to  the  obese. 

Bornstein1  finds  that  during  a  period  of  thirteen  days  he 
can  add  8.3  grams  of  protein  to  his  body  and  oxidize  90  grams 
of  body  fat  daily  when  ingesting  a  mixed  diet  containing  1600 
calories  with  118  grams  of  protein.  Such  a  diet  contains  a 
fuel  value  less  than  the  requirement  of  his  organism  (p.  279). 

1  Bornstein:   "Berliner  klinische  Wochenschrift,"  1904,  xli,  1192. 


THE   INFLUENCE   OF   PROTEIN  FOOD 


155 


This  cannot  be  accomplished  without  carbohydrate  in  the 
diet,  for  Thomas1  finds  that  when  a  man  is  given  protein  alone, 
administered  in  fractional  portions  every  two  hours  even  to 
the  extent  of  double  the  quantity  of  protein  destroyed  in 
fasting,  nitrogen  equilibrium  cannot  be  obtained.  This  ex- 
periment is  given  below;  500  grams  of  meat  contained  18.4 
grams  of  nitrogen,  corresponding  to  about  115  grams  of  protein: 


Day 

6 

7             3 

10 

11 

12 

|3 

14 

15 

7.64 
-8.16 

8.63 

g.78     12.90 

—  10.00   —4.79 

8.63 
13.46 
-4-79 

8.63 
14.42 
-6.31 

I5-S4 
16.81 
-1.79 

17.27 
18.92 
—  2.17 

18.39 
20.85 
-2.97 

18.40 
21.30 
—3-62 

18.39 
21.52 

±  N  to  body 

-3.64 

If  the  quantity  of  meat  ingested  be  steadily  increased  after 
nitrogenous  equilibrium  has  been  reached,  the  protein  metab- 
olism will  gradually  increase,  nitrogenous  equilibrium  will  be 
established  at  higher  and  higher  levels,  and  there  will  be  a  cor- 
responding diminution  in  the  amount  of  fat  burned.  This  was 
shown  in  1862  in  the  following  experiment  of  Voit,2  who 
gave  different  quantities  of  meat  to  a  large  dog  weighing  30 
kilograms : 

INFLUENCE  OF  INGESTING  INCREASING  QUANTITIES  OF  MEAT 

Weights  are  in  Grams 


Meat 
Ingested. 

Flesh 
Destroyed. 

Gain  or 

Loss  OF 

Body  Flesh. 

Gain  or 

Loss  of 

Body  Fat. 

02 

CO2 

R.  Q. 

0 

SOO 

1000 

ISOO 

1800 

2000 

2S°0 

165 

599 
1079 
1500 

1757 
2044 
2512 

-165 

-99 

-79 

0 

+43 
-44 
—  12 

-95 
-47 
-19 

+4 

+  1 

+58 

+  57 

33° 
341 
453 
487 

5i7 

327 
356 
463 
547 
656 
604 
783 

.72 
.76 

•74 
.81 

.84 

Nitrogen  equilibrium  existed  after  the  ingestion  of  1500 
grams  of  meat  and  there  was  also  no  loss  of  body  fat  (carbon 
equilibrium).     When   2000  grams  and  even  2500  grams  of 


1  Thomas:   "Archiv  fur  Physiologie,"  1910  Suppl.,  p. 

2  Voit:   "Stoffwechsel,"  1881,  p.  117. 


249. 


156  SCIENCE   OF   NUTRITION 

meat  were  supplied  it  was  all  destroyed,  as  was  indicated  by 
the  amount  of  nitrogen  in  the  urine,  but  a  certain  quantity  of 
carbon  belonging  to  the  ingested  protein  was  not  eliminated  in 
the  respiration,  but  was  retained  in  the  body.  This  carbon 
Pettenkofer  and  Voit  believed  to  have  been  laid  up  in  the  body 
in  the  form  of  fat. 

The  respiratory  quotient  in  the  foregoing  series  gradually 
rises,  as  would  be  expected  from  the  increasing  prominence 
of  the  protein  in  the  metabolism  (p.  60).  Meat  alone  will 
therefore  support  a  dog.  Rubner1  says  that  a  man  cannot 
live  on  meat  alone,  not  because  the  intestinal  canal  cannot 
digest  it,  but  because  of  the  physical  limitations  of  the  ap- 
paratus of  mastication.  A  dog  weighing  10  kilograms  may 
ingest  1000  grams  of  chopped  meat  in  forty-five  seconds,  while 
a  man  requires  between  five  and  ten  minutes  rapidly  to  cut 
and  partake  of  200  grams  of  good  sirloin  steak. 

A  subject  of  interest  in  considering  the  value  of  protein  in 
metabolism  is  that  of  the  value  of  gelatin.  Gelatin  is  an  artifi- 
cial derivative  of  collagen,  an  albuminoid  largely  found  in  the 
skeletal  structure  of  animals.  Gelatin  contains  very  nearly 
the  same  quantity  of  nitrogen  as  protein ;  it  breaks  up  on  chem- 
ical treatment  into  the  same  amino-acids,  except  that  it  does 
not  yield  tyrosin,  cystin,  and  tryptophan.  In  the  diabetic, 
gelatin  yields  the  same  amount  of  sugar  as  does  protein.2 
To  what  extent  gelatin  may  take  the  place  of  protein  in  the 
body's  metabolism  has  long  been  the  subject  of  inquiry. 

It  was  shown  first  by  Bischoff  and  Voit3  that  no  matter 
how  much  gelatin  was  ingested,  it  was  always  completely 
burned,  and  some  of  the  body's  protein  in  addition.  There- 
fore gelatin  never  builds  up  new  tissue,  although  it  may  some- 
what diminish  tissue  waste.  Gelatin  may  be  formed  from 
protein  in  the  body,  but  it  cannot  be  reconverted  into  protein 
nor  act  like  protein  in  metabolism.     Kirchmann,4  working 

1  Rubner:    von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1903,  i,  42. 

2  Reilly,  Nolan,  and  Lusk:  "American  Journal  of  Physiology,"  1898,  i,  395. 

3  Voit:    Hermann's  Handbuch,  "Stoffwechsel,"  1881,  p.  396. 

4  Kirchmann:    "Zeitschrift  fur  Biologie,"  1900,  xl,  54. 


THE  INFLUENCE  OF  PROTEIN  FOOD  157 

in  the  laboratory  of  Erwin  Voit?  has  shown  to  what  extent 
gelatin  spares  protein  in  metabolism.  If  one  takes  the  an^ount 
of  protein  metabolism  in  starvation  as  one,  then  the  ingestion 
of  about  the  same  quantity  of  gelatin  reduces  the  body's 
protein  waste  23  per  cent.,  and  if  eight  times  this  amount  of 
gelatin  be  given,  the  tissue  waste  may  be  reduced  35  per 
cent.  In  other  words,  the  ingestion  of  7.5  per  cent,  of  the 
total  heat  requirement  of  the  organism  in  the  form  of  gelatin 
spares  23  per  cent,  of  the  body's  protein,  while  the  ingestion 
of  60  per  cent,  of  the  requirement  will  only  cause  a  decrease  of 
35  per  cent,  in  protein  waste.  Krummacher1  showed  that 
the  ingestion  of  the  full  heat  requirement  of  the  animal  in 
the  form  of  gelatin  reduced  the  fasting  protein  metabolism 
by  only  37.5  per  cent.  It  is  evident  that  no  matter  how 
much  gelatin  be  given,  tissue  protein  continues  to  be  destroyed, 
and  it  is  also  evident  that  a  small  quantity  of  gelatin  has  almost 
as  great  an  effect  as  a  large  quantity. 

An  extremely  interesting  experiment  of  Kauffmann2  shows 
that  when  the  lacking  tyrosin,  cystin,  and  tryptophan  are 
mixed  with  gelatin  in  the  proportions  in  which  they  occur  in 
true  protein,  and  are  given  to  a  dog  or  to  a  man,  nitrogen 
equilibrium  may  be  established.  Abderhalden3  confirms  this 
in  similar  experiments. 

It  is  evident,  therefore,  that  the  value  of  the  various  pro- 
teins in  nutrition  may  depend  upon  their  constituent  amino- 
acids,  and  this  will  be  considered  on  another  occasion  (see  p. 

37i)- 

It  appears  that  protein  bodies  must  be  broken  up  into 

amino-acids  before   absorption   in  the  intestine  (p.  79).     If 

this  be  true,  then  ingestion  of  the  cleavage  products  of  protein 

should  maintain  nitrogen  equilibrium  in  the  same  way  as  the 

ingestion  of  meat.     The  first  experiments  in  this  direction 

were  done  by  Loewi,4  who  gave  a  dog  pancreas  which  had  been 

1  Krummacher:   "Zeitschrift  fur  Biologie,"  1901,  xlii,  242. 

2  Kauffmann:   "Pfkiger's  Archiv,"  1905,  cix,  440. 

3  Abderhalden:    "Zeitschrift  fur  physiologische  Chemie,"  1912,  lxxvii,  22. 

4  Loewi:    "Archiv  fur  ex.  Path,  und  Pharm.,"  1902,  xlviii,  303. 


158  SCIENCE    OF   NUTRITION 

self-digested  until  all  the  protein  had  been  converted  into 
amino-acids,  as  was  indicated  by  the  almost  complete  dis- 
appearance of  the  biuret  reaction.  Fat  and  carbohydrates 
were  given  with  the  digest,  and  nitrogen  equilibrium  was 
obtained  and  even  nitrogen  retention  accomplished.  Thus, 
in  one  experiment  covering  a  period  of  eleven  days,  proteolytic 
digestive  products  containing  an  average  of  6.08  grams  of 
nitrogen  were  given  daily,  of  which  only  5.19  grams  were 
eliminated  in  the  excreta,  while  the  balance,  or  0.89  gram  of 
nitrogen,  was  retained  in  the  body  of  the  animal.  This 
amounted  to  9.79  grams  of  nitrogen  in  eleven  days.  Ac- 
companying this  nitrogen  retention  was  one  of  0.649  gram  of 
phosphoric  acid  (P2O5),  an  amount  larger  than  was  necessary 
for  the  upbuilding  of  new  tissue  from  the  nitrogen  compounds 
retained.  Loewi  concluded  that  he  had  demonstrated  the 
synthesis  of  new  protein  within  the  organism. 

Henderson  and  Dean1  confirmed  Loewi  by  finding  that 
they  could  obtain  nitrogen  equilibrium  by  feeding  a  dog  with 
the  cleavage  products  of  meat  produced  by  treatment  with 
sulphuric  acid. 

Abderhalden  and  Ron  a2  find  that  mice  live  on  casein  split 
with  pancreatin  as  long  as  they  do  on  casein  alone;  whereas 
they  die  much  earlier  if  the  casein  has  been  submitted  to  peptic 
and  then  pancreatic  digestion,  or  if  it  has  been  broken  up  by 
acid  hydrolysis.  Henriques  and  Hansen3  also  find  that  casein 
broken  up  by  acid  will  not  maintain  nitrogen  equilibrium  in 
rats,  but  that  if  the  pancreas  of  the  ox  and  a  small  piece  of  the 
intestine  of  the  dog  (to  furnish  erepsin)  be  digested  for  two 
months  at  400,  and  the  resulting  material  given  to  rats, 
nitrogen  equilibrium  will  be  maintained.  The  authors  further 
find  that  the  mono-amino-acid  fraction  (the  filtrate  after 
precipitation  with  phosphowolframic  acid)  and  also  the 
alcoholic  extract  of  the  last-named  digest  maintain  rats  in 

1  Henderson  and  Dean:    "American  Journal  of  Physiology,"  1903,  ix,  386. 

2  Abderhalden  and  Rona:  "Zeitschrift  fur  physiologische  Chemie,"  1904, 
xlii,  528. 

3  Henriques  and  Hansen:   Ibid.,  1905,  xliii,  417. 


THE  INFLUENCE  OF  PROTEIN  FOOD  1 59 

nitrogen  equilibrium.  The  residue  left  after  alcoholic  ex- 
traction will  not  do  so. 

Abderhalden  and  Rona1  have  accomplished  a  most  interest- 
ing experiment  upon  a  dog.  The  animal  was  given  daily  a 
constant  quantity  of  non-nitrogenous  foods  which  were:  fat, 
25  grams;  starch,  50  grams;  cane-sugar,  10  grams;  glucose, 
5  grams.  The  dog  was  brought  into  nitrogen  equilibrium  by 
giving  him  meat  containing  2  grams  of  nitrogen.  Then  for  this 
were  substituted  the  amino  cleavage  products  of  casein,  pro- 
duced by  pancreatic  digestion  and  also  containing  2  grams  of 
nitrogen.  During  sixteen  days  on  this  diet  there  was  an 
average  daily  gain  of  o.  1 2  gram  of  nitrogen  by  the  dog.  Then 
casein  hydrolized  by  acid  and  containing  2  grams  of  nitrogen 
was  administered  for  ten  days,  during  which  time  the  dog  lost 
0.48  gram  of  nitrogen  daily.  Amino  products  prepared  after 
this  fashion  will,  therefore,  not  preserve  nitrogen  equilibrium. 
Lastly,  the  diet  was  continued  without  any  nitrogenous  food. 
The  daily  waste  of  body  nitrogen  was  then  0.53  gram.  The 
loss  was  the  same  as  when  the  casein  hydrolized  by  acid  was 
ingested,  indicating  that  this  particular  array  of  cleavage  prod- 
ucts had  no  protecting  power  over  the  body  protein. 

Henriques2  has  hydrolized  protein  by  digesting  it  with 
trypsin  and  erepsin  and  then  treating  with  20  per  cent, 
sulphuric  acid  on  the  water-bath.  The  resulting  material 
consists  entirely  of  amino-acids  with  no  admixture  of  poly- 
peptids,  and  if  it  still  gives  a  pronounced  tryptophan  reaction 
it  will  support  the  organism  in  nitrogen  equilibrium.  In  the 
absence  of  the  single  amino-acid  tryptophan,  nitrogen  equilibrium 
cannot  be  attained. 

To  complete  the  story,  the  work  of  Abderhalden3  must  be 
recited.  Nitrogen  equilibrium  and  even  nitrogen  retention 
were  established  in  a  dog  when  the  diet  contained  instead  of 
protein  the  following  mixture  of  pure  amino-acids:  Glycocoll 

1  Abderhalden  and  Rona:  "Zeitschrift  fur  physiologische  Chemie,"  1905, 
xliv,  198. 

2  Henriques:   Ibid.,  1907,  liv,  406. 

3  Abderhalden:   "Zeitschr.  f.  physiol.  Chem.,"  1912,  lxxvii,  22. 


l6o  SCIENCE   OF   NUTRITION 

5  grams,  d-alanin  10  grams,  1-serin  3  grams,  1-cystin  2  grams, 
d-valin  5  grams,  1-leucin  10  grams,  d-isoleucin  5  grams, 
1-aspartic  acid  5  grams,  d-glutamic  acid  15  grams,  1-phenyl- 
alanin  5  grams,  1-tyrosin  5  grams,  1-lysin  5  grams,  d-arginin  5 
grams,  1-prolin  10  grams,  1-histidin  5  grams,  and  1-tryptophan 
5  grams.  This  mixture  weighed  100  grams  and  contained 
13.87  grams  of  nitrogen.  It  is  not  unlike  ox  muscle  in  rela- 
tive composition  (see  p.  77). 

It  is  therefore  proved  that  amino  bodies  resulting  from 
certain  proteolytic  cleavages  may  be  the  equivalent  in  metab- 
olism of  ingested  protein  itself. 

In  practical  dietetics  these  substances  can  have  little  value, 
as  they  tend  to  produce  diarrhea,  as  do  also  albumoses  and 
peptones  when  given  in  any  considerable  quantity.1  As  illus- 
trating this  Cronheim2  finds  that  though  "Somatose"  is  more 
digestible  than  meat,  still  over  30  grams  are  undesirable  in 
the  daily  diet  of  a  man. 

It  is  certain  that  if  there  be  a  new  construction  of  protein 
in  the  body  from  the  amino-acids  formed  in  digestion  such 
new  proteins  are  characteristic  of  the  organism,  and  do  not 
possess  the  properties  of  the  proteins  originally  ingested.  To 
illustrate  this  Abderhalden  and  Samuely3  gave  to  a  horse  1 500 
grams  of  gliadin,  a  vegetable  protein  which  contains  36.5  per 
cent,  of  glutamic  acid.  They  wondered  if  the  ingestion  of 
such  a  protein  would  in  any  way  modify  the  composition  of  the 
proteins  of  the  blood-serum,  of  serum  globulin  which  under 
ordinary  circumstances  contains  8.5  per  cent.,  and  of  serum 
albumin  which  contains  7.7  per  cent,  of  glutamic  acid.  Their 
results  were  as  follows : 

INFLUENCE  OF  GLIADIN  INGESTION  ON  THE  PERCENTAGE  OF 
GLUTAMIC  ACID  IN  THE  SERUM  PROTEINS  OF  THE  HORSE 

After  Ingesting 


Normal 

After  Fasting 

1500  G.  Gliadin. 

Experiment. 

Day. 

7  or  8  Days. 

Day  1.                  Day  2. 

I 

...    8.85 

8.20 

7.88                    8.25 

II 

. .  ■    9-52 

8.52 

8.00 

1  Voit,  F.:   "Munchener  med.  Wochenschrift,"  1899,  xlvi,  172. 

2  Cronheim:    "Pfliiger's  Archiv,"  1904,  cvi,  17. 

3  Abderhalden  and  Samuely:     "Zeitschrift  fiir  physiologische  Chemie," 
1905,  xlvi,  193. 


THE  INFLUENCE  OF  PROTEIN  FOOD  l6l 

It  is  evident  that  gliadin,  which  contains  so  large  a  pro- 
portion of  glutamic  acid,  is  without  influence  on  the  composi- 
tion of  the  blood-serum.  Abderhalden  conceived  that  such 
proportions  of  the  amino-acids  within  the  gliadin  complex 
as  are  available  for  the  formation  of  new  serum  albumin  and 
serum  globulin  were  used  for  the  generation  of  these  proteins. 
Evidence  that  amino-acids  enter  the  blood-stream  directly 
from  the  intestinal  tract  has  already  been  submitted.  Fur- 
thermore, Henriques  and  Anderson1  have  administered  con- 
tinuous intravenous  injections  of  meat  hydrolized  with  trypsin 
and  erepsin  to  goats  which  had  survived  the  operation  of 
extirpating  the  intestines,  and  have  noted  nitrogen  retention. 
From  this  they  conclude  that  the  intestine  is  not  necessary 
for  protein  regeneration. 

It  has  already  been  stated  (p.  74)  that  if  the  serum  of  a  dog 
be  injected  into  the  blood-vessels  of  another  dog  the  nitrogen 
of  it  will  be  eliminated  in  the  urine.  This  is  also  true  of  pro- 
teins foreign  to  the  organism,  and  these  likewise  act  in  a  toxic 
manner  to  destroy  body  protein.  Thus  Mendel  and  Rock- 
wood2  have  shown  that  if  edestin,  a  pure  crystalline  protein 
prepared  from  hemp  seed,  be  injected  intravenously  into  a 
fasting  dog,  there  is  for  two  days  a  metabolism  of  protein  which 
is  much  greater  than  that  of  former  days  plus  that  of  the 
edestin  administered.  The  same  truth  holds  when  casein  is 
injected.  Similar  injection  of  horses'  serum  into  dogs  ap- 
pears to  have  no  toxic  action  (Rona  and  Michaelis3).  This 
work  is  of  interest  in  connection  with  the  subject  of  anaphy- 
laxis, called  also  the  Theobald  Smith  phenomenon,  which  has 
been  especially  investigated  by  Rosenau  and  Anderson. 
Injections  of  a  protein  foreign  to  the  organism  render  the  body 
sensitive  to  a  second  injection  of  the  same  protein.  Large 
or  small  amounts  of  foreign  protein  may  be  injected  in  the 

1  Henriques  and  Anderson:  "Zeitschrift  fur  physiologische  Chemie,"  19 14, 
xcii,  194. 

2  Mendel  and  Rockwood:  "American  Journal  of  Physiology,"  1904,  xii, 
350. 

3  Rona  and  Michaelis:  "Pfluger's  Archiv,"  1908,  cxxi,  163;  1908,  cxxiii,  406. 


1 62  SCIENCE   OF   NUTRITION 

first  instance  without  intoxication,  but  if  the  animal  oe  once 
"sensitized"  a  small  amount  of  the  same  protein  will  ter- 
minate the  animal's  existence.  It  has  recently  been  stated 
by  Wells1  that  the  injection  of  so  minimal  an  amount  as 
nnruFoo  gram  of  pure  crystalline  egg-albumin  will  "sensitize" 
a  guinea-pig  so  that  a  subsequent  injection  into  the  blood 
of  tV  milligram  of  the  same  substance  is  lethal,  although  such 
a  dose  given  in  the  first  instance  would  not  have  injured  the 
animal.  It  is  evident,  therefore,  that  the  alimentary  canal 
cannot  allow  the  passage  of  proteins  without  changing  them. 
This  also  explains  the  complete  immunity  of  the  organism  to 
snake  venom  which  has  been  swallowed. 

The  effect  of  copious  drinking  of  water  upon  protein  metab- 
olism has  been  made  the  subject  of  various  studies.  A  small 
increase  in  nitrogen  elimination  has  usually  been  noted.  This 
was  first  established  by  Voit,  who  explained  it  as  due  to  an 
increased  circulation  which  influenced  the  flow  of  the  intra- 
cellular fluids.  Heilner2  has  shown  that  giving  2000  c.c.  of 
water  to  a  fasting  dog  on  two  successive  days  raises  his 
urinary  nitrogen  from  3.15  grams  to  4.09  and  3.58  grams  on 
the  two  days  of  water  ingestion,  and  then  the  nitrogen  excre- 
tion falls  to  2.22  and  2.62  on  the  following  days.  In  this 
experiment  the  carbon  dioxid  excretion  was  very  slightly 
increased  and  the  temperature  of  the  dog  was  not  affected. 
The  quantity  of  urine  rose  from  90  to  2050  c.c. 

Straub3  found  that  an  extra  ingestion  of  2000  c.c.  of  water 
in  a  man  who  was  in  nitrogen  equilibrium  on  a  diet  containing 
20.56  grams  of  nitrogen  had  no  effect  on  protein  metabolism; 
whereas  Hawk,4  who  gave  less  protein  nitrogen  but  more  water, 
found  that  the  ingestion  of  4500  c.c.  of  water  caused  the  urinary 
nitrogen  to  rise  from  11.03  to  I2-4-8  on  the  first  day,  and  11.82 
on  the  second  day,  with  a  fall  to  10.91  grams  on  the  suc- 

1  Wells:  Proceedings  of  the  Society  for  Experimental  Biology  and  Medicine, 
1908,  vi,  1. 

2  Heilner:   "Zeitschrift  fur  Biologie,"  1906,  xlvii,  541. 

3  Straub:   Ibid.,  1899,  xxxvii,  527. 

4  Hawk:    "University  of  Pennsylvania  Medical  Bulletin,"  March,  1905. 


THE  INFLUENCE  OF  PROTEIN  FOOD  1 6^ 

ceeding  day  when  no  water  was  given.  Hawk  interprets  the 
action  of  copious  water  drinking  as  twofold :  first,  to  cause  a 
.removal  of  any  accumulation  of  nitrogenous  decomposition 
products  from  the  organism,  as  was  indicated  by  the  greater 
increase  of  12.8  per  cent,  in  the  nitrogen  elimination  of  the 
first  day;  and,  second,  to  cause  a  true  increase  in  protein 
metabolism,  as  was  indicated  by  the  smaller  increase  of  6.8 
per  cent,  on  the  second  day  of  water  ingestion. 

Abderhalden  and  Bloch1  have  given  a  fixed  diet  to  a  person 
suffering  from  alkaptonuria  (see  p.  178)  and  on  one  of  the  days 
of  the  experiment  have  caused  him  to  ingest  5  liters  of  water. 
The  results  of  their  analyses  gave  the  following  figures: 


N  Balance. 

N  IN 

Urine. 

Homogentisic 
Acid. 

rmal  Food +1.36 

"    +  5  L.  Water  —2.19 
"    +1-47 

18.2 

21-75 

18.09 

10.52 
10/18 

IO.27 

Abderhalden  believes  that  the  constancy  of  the  output  of 
homogentisic  acid  indicates  a  constancy  of  protein  metabolism 
throughout,  whereas  the  rise  in  total  nitrogen  elimination  in 
the  urine  represents  a  washing  out  of  the  nitrogenous  end- 
products  as  a  result  of  the  large  ingestion  of  water. 

One  of  the  striking  characteristics  of  starvation  metabolism 
was  shown  to  be  its  extreme  regularity  from  hour  to  hour  and 
from  day  to  day.  What,  then,  is  the  hour-to-hour  metabolism 
after  meat  ingestion? 

The  classical  experiments  of  Voit2  and  of  Feder3  have  been 
more  fully  worked  over  by  Gruber.  Gruber4  fed  a  dog  with 
500,  1000,  and  1500  grams  of  meat  on  different  days.  He 
collected  the  urine  every  two  hours  after  the  meal  and  deter- 
mined the  nitrogen  output.  The  curves  of  nitrogen  elimi- 
nation under  these  circumstances  are  as  follows : 

1  Abderhalden  and  Bloch:  "Zeitschrift  fiir  physiologische  Chemie,"  1907, 
liii,  464. 

2  Voit:   "Physiologische  Untersuchungen,"  Augsburg,  1857,  p.  42. 

3  Feder:   "Zeitschrift  fiir  Biologie,"  1881,  xvii,  541. 

4  Gruber:   Ibid.,  1901,  xlii,  421. 


1 64 


SCIENCE   OF   NUTRITION 
JV.in  jrams  per  Zhrs. 


s 

* 

/ 

(, 

J 

s 

\ 

\ 

\ 

t 

/ 

V 

"^ 

/ 

1 

\ 

J,// 

A~ 

-> 

f 

\ 

\ 

*/ 

1 

V 

\ 

J 

\ 

■ 

O    2     4      6     S 


10    )Z     I*    lb    18     10    ZZ     Z& 

Hours 


Fig.  12. — i,  After  500  g.  meat  +  50  g.  fat  +  350  c.c.  water;  2,  after  1000  g. 
meat  +  200  c.c.  water;  3,  after  1500  g.  meat  +  500  c.c.  water.  On  each  of  these 
days  the  animal  was  in  nitrogen  equilibrium. 

It  is  evident  that  there  is  an  early  elimination  of  protein 
nitrogen  which  here  reaches  a  maximum  between  five  and  seven 
hours  after  feeding,  and  that  the  hour  of  the  maximum  excre- 
tion is  delayed  by  increasing  the  quantity  of  meat  ingested. 

It  is  apparent,  therefore,  that  the  protein  metabolism  as 
illustrated  by  the  curve  of  nitrogen  elimination  is  quite 
different  from  its  even  metabolism  in  starvation. 

Haas1  in  experiments  on  man  finds  that  the  curve  of  nitro- 
gen elimination  after  a  breakfast  consisting  of  milk,  bread, 
butter,  and  cheese  always  shows  two  maxima,  the  first  in  the 
second  hour  and  the  second  in  the  fifth.  The  first  rise  in  the 
curve  is  due  to  the  removal  of  nitrogenous  end-products  already 

lHaas:  "Biochemische  Zeitschrift,"  1908,  xii,  203. 


THE  INFLUENCE  OF  PROTEIN  FOOD  1 65 

in  the  system  and  is  caused  by  the  early  absorption  of  liquids 
taken  with  the  food.  The  second  rise  corresponds  to  the 
absorption  of  food  protein.  Haas  believes  this  to  be  the  true 
explanation,  because  if  diuresis  be  first  induced  by  drinking 
tea,  with  a  consequent  washing  out  of  urea  from  the  body, 
then  partaking  of  breakfast  no  longer  causes  so  high  a  primary 
rise  of  nitrogen  elimination,  nor  is  the  total  elimination  so 
great  as  in  the  experiments  without  preliminary  diuresis. 
The  experiment  shows  that  for  short  periods  the  nitrogen 
excretion  is  not  a  true  index  of  urea  production.  Severe 
muscular  work  has  no  influence  upon  the  character  of  the  curve 
described  except  when  the  quantity  of  urine  produced  is 
diminished,  in  which  case  the  urea  elimination  is  also  reduced. 

Confirming  Albarran,1  Barringer  and  Barringer2  note  that 
the  volumes  and  the  nitrogen  content  of  the  urine  from  the 
two  kidneys  are  almost  identical. 

Urea  in  the  organism  undergoes  no  chemical  change;  there 
is  no  reversible  reaction  in  the  sense  of  ammonia  formation.3 
When  urea  is  retained  in  the  body  it  is  found  widely  distrib- 
uted in  all  the  tissues  excepting  fatty  tissue;  if  it  be  admin- 
istered intravenously  to  a  dog  diffusion  to  all  parts  of  the  body 
is  complete  in  a  few  minutes.4  A  concentration  of  1.2  per 
cent,  may  sometimes  be  reached  in  the  dog,  though  one  of  over 
1  per  cent,  is  usually  fatal. 

The  amount  of  urea  excretion  is  found  to  be  closely  parallel 
to  the  urea  concentration  of  the  blood.  This  relation  was 
formulated  in  Ambard's  laws  of  urea  elimination.5 

d)  When  the  concentration  of  urea  in  the  urine  is  constant 
the  quantity  of  urea  excreted  in  the  urine  varies  propor- 
tionately to  the  square  of  the  concentration  of  urea  in  the 
blood. 

(2)  When  the  concentration  of  urea  in  the  blood  remains 

1  Albarran:    "Exploration  des  fonctions  renales,"  Paris,  1905,  p.  329. 

2  Barringer  and  Barringer:  "Amer.  Jour,  of  Physiology,"  1910-n,  xxvii, 
119. 

3  Janney:     "Zeitschrift  fur  physiologische  Chemie,"  1911-12,  lxxvi,  99. 

4  Marshall  and  Davis:    "Journal  of  Biological  Chemistry,"  1914,  xviii,  53. 
6  Ambard:    "Comptes  rendus  societe  de  biologie,"  19 10,  lxii,  506. 


1 66 


SCIENCE   OF   NUTRITION 


constant  the  quantity  excreted  in  the  urine  varies  inversely  as 
the  square  root  of  the  concentration  in  the  urine. 

From  these  laws  Ambard's  coefficient  or  constant  for  the 
urea  elimination  through  the  kidney  of  human  subjects  was 
evolved.  Arbitrary  standards  of  normal  weight,  such  as  70 
kilograms,  and  of  urea  excreted  in  twenty-four  hours,  such  as 
25  grams,  were  adopted  in  the  formula,  which  is  as  follows: 

Ur 


v; 


=  K  or  Constant  of  Ambard. 


J70 
Wt 


c 

25 


Ur  =  Urea  per  liter  of  blood  in  grams. 

D  =  Urea  in  urine  in  twenty-four  hours  in  grams. 
Wt  =  Weight  of  patient  in  kilograms. 

C  =  Concentration,  or  grams  urea  per  liter  of  urine. 

Ambard  found  the  constant  in  normal  individuals  varied 
between  0.06  and  0.07.  McLean,1  who  has  used  more  ac- 
curate methods  for  measuring  urea,  finds  the  constant  to  be 
nearer  0.08,  with  wider  variations  than  French  observers  found. 
This  coefficient  is  being  applied  to  determine  kidney  efficiency 
in  renal  disease.  When  the  coefficient  is  found  to  be  much 
increased,  then  urea  is  being  retained  by  the  organism  on 
account  of  renal  insufficiency. 

Citing  from  McLean  and  Selling,2  the  following  results 
may  be  given : 


Person. 


F.  C.  M. 

F.  C.  M. 

H.  K.  A. 
B. 


Time. 


Forty-five  minutes  after 
10  g.  urea 

Three  days  low  protein 
diet 

After  heavy  dinner. .  .  . 

Nephritic 


Urea  N 

In  Urine. 

In  Blood. 

In  24  Hours. 

Per  Liter. 

Mg. 

Grams. 

Grams. 

24 

24.6 

16.4 

14 

6.9 

9-7 

22 

11.4 

11.6 

29 

9.6 

7.6 

Ambard's 
Coeffi- 
cient. 


0.068 

0.085 
0.088 
0.150 


1  McLean:    "Journal  of  Exp.  Medicine,"  1915,  xxii,  212. 

2  McLean  and  Selling:    "Journal  of  Biological  Chemistry,"  1914,  xix,  31. 


THE  INFLUENCE  OF  PROTEIN  FOOD 


167 


In  some  interesting  work  Pepper  and  Austin1  find  that  after 
giving  900  grams  of  meat  to  a  dog  the  non-protein  nitrogen  in 
the  blood  rises  rapidly  from  20  to  60  mg.  per  100  ex.,  and  the 
urinary  nitrogen  rises  from  0.15  gram  to  1.1  grams  per  hour. 

It  is  evident  from  this  analysis  that  the  curve  of  nitrogen 
elimination  is  not  an  exact  indicator  of  the  time  relations  of 
the  breaking  up  of  ammo-acids  in  the  body,  for  a  part  of 
the  urea  formed  accumulates  in  the  blood  and  is  not  at  first 
eliminated  in  the  urine,  and  too  low  a  protein  metabolism  may 
thus  in  error  be  computed.  Later,  with  a  diminished  absorp- 
tion of  amino-acids  and  diminished  production  of  urea,  the 
excess  which  is  not  attributable  to  the  metabolism  of  the 
moment  is  eliminated  from  the  blood,  and  the  urinary  nitrogen 
of  these  hours  will  give  too  high  figures  if  used  to  compute  the 
protein  metabolism  of  short  periods  (see  p.  173). 

It  may  here  be  noted  that  the  elimination  of  sodium 
chlorid  follows  Ambard's  laws  in  the  behavior  of  that  quantity 
which  is  in  excess  of  5.62  grams  of  NaCl  per  liter  of  blood- 
plasma2  (see  p.  523)  which  is  the  threshold  value  of  elimina- 
tion by  the  kidney. 

It  was  shown  by  Rubner,3  who  gave  washed  meat  contain- 
ing 24.72  grams  of  nitrogen  to  a  dog  daily  for  three  days,  that 
the  sulphur  elimination  preceded  that  of  the  nitrogen,  while 
that  of  phosphorus  followed  it.  The  results  of  the  third  day, 
at  a  time  when  the  dog  was  essentially  in  nitrogen  equilibrium, 
are  divided  into  six  hourly  periods  and  are  given  below: 


Period. 

S. 

N. 

N 
S 

Of  100  Per  Cent,  were  Excreted 

S. 

N. 

P. 

I 

II 

Ill 

IV 

0.448 
0.387 

0-257 
0.131 

5-57 
8.94 
5-32 
2.66 

12.4 
23.1 
20.7 
20.3 

36.7 

3i-7 
21. 1 
10.5 

24.8 
39-8 
23-6 
11.8 

16.0 

33-4 

18.5 

1.223 

22.49 

18.4 

1  Pepper  and  Austin:    "Journal  of  Biological  Chemistry,"  1915,  xxii,  81. 

2  For  discussion,  see  McLean,  loc.  cit. 

3  Rubner:   "Gesetze  des  Energieverbrauchs,"  1902,  368. 


1 68  SCIENCE   OF   NUTRITION 

The  elimination  of  sulphur  more  rapidly  than  nitrogen  after 
meat  ingestion  has  been  confirmed  by  von  Wendt1  in  man.  It 
appears  that  the  end-products  of  the  metabolism  of  sulphur- 
containing  cystin  appear  in  the  urine  more  rapidly  than  urea, 
while  phosphorus,  which  is  an  end-product  of  nuclein  metab- 
olism, makes  its  appearance  more  slowly. 

Two  explanations  of  the  early  elimination  offer  themselves : 
one,  that  the  sulphur-containing  cystin  radicle  is  oxidized  with 
exceptional  ease;  two,  that  the  sulphur  compounds  may  not 
accumulate  in  the  organism  as  does  urea.  Variations  in  the 
rate  of  sulphur  elimination  may  also  undoubtedly  be  in- 
fluenced by  bacterial  activity. 

If  in  man  various  proteins  be  added  to  an  already  suffi- 
cient mixed  diet  (superposition  experiments),  the  rate  of  de- 
struction of  the  added  protein  as  indicated  by  the  extra  N 
eliminated  in  the  urine  varies  with  the  character  of  the  protein. 
Such  experiments  were  first  devised  by  Falta,2  who  established 
the  following  classification  of  proteins  in  the  order  of  the 
rapidity  of  their  destruction:  a,  gelatin,  casein,  serum  albu- 
min, fibrin;  b,  blood  globulin;  c,  hemoglobin;  d,  egg-albumin. 
Hamalainen  and  Helme3  continued  these  experiments  and 
they  also  investigated  the  elimination  of  sulphur  and  phos- 
phorus. They  gave  a  man  weighing  66  kilograms  a  diet 
containing  3650  calories  and  5  grams  of  nitrogen.  On  this 
diet  they  superimposed  on  different  days  the  following  amounts 
of  proteins: 

800  g.  white  of  egg  =  14.40  g.  N  +  1.56    g.  S. 

57  g.  proton  =     6.94  g.  N  -f-  0.419  g.  S. 

320  g.  veal  =  13.44  g-  N  +  0.832  g.  S. 

and  noticed  the  time  of  the  elimination  of  nitrogen,  sulphur, 
and  phosphorus  through  the  kidney.  It  was  six  days  before 
all  the  nitrogen  of  the  ingested  white  of  egg  was  eliminated, 
whereas  that  in  veal  and  proton  required  only  two  or  three 
days.     This  is  evident  from  the  following  table: 

1  von  Wendt:    "Skan.  Archiv  fur  Physiologie,"  1905,  xvii,  211. 

2  Falta:    "Deutsches  Archiv  fur  klinische  Medizin,"  1906,  lxxxvi,  517. 

3  Hamalainen  and  Helme:   "Skan.  Archiv  fur  Physiologie,"  1907,  xix,  182. 


THE  INFLUENCE  OF  PROTEIN  FOOD 


169 


DAILY  PERCENTAGE  ELIMINATION  OF  THE  NITROGEN,  SUL- 
PHUR, AND  PHOSPHORUS  OF  INGESTED  PROTEIN  SUPER- 
IMPOSED 'ON   AN   ADEQUATE   DIET 


Egg-white. 

Proton. 

Veal. 

Day 

N. 

s. 

N. 

S. 

N. 

S. 

P. 

1 

21 

41.4 

64 

90 

56 

74.2 

60 

i 

21 

32.2 

14.4 

4-3 

26 

17.8 

8  0 

24 
16 

3 

13 
13 

18 

4 

11 

5 

14 

5-5 

6 

11 

2.4 

The  rapidity  of  the  sulphur  elimination  is  everywhere 
noticeable.  The  "nitrogen  lag"  in  the  case  of  white  of  egg  is 
pronounced  and  may  be  due  to  the  retention  of  peptids  which 
are  only  slowly  metabolized,  or  it  may  be  due  to  the  retention 
of  amino-acids  themselves. 

Mendel  and  Lewis1  suggest  that  the  flattened  curves  of 
nitrogen  elimination  found  after  the  ingestion  of  egg-white  or 
ovalbumin  may,  to  a  great  extent,  be  explained  by  a  difference 
in  the  rate  and  completeness  of  the  absorption  of  these  sub- 
stances when  contrasted  with  the  behavior  of  meat,  casein, 
ovovitellin,  edestin,  gliadin  and  gelatin,  between  which  little 
difference  could  be  observed. 

Cathcart  and  Green2  have  superimposed  egg-albumin  upon 
a  vegetarian  diet  in  man.  In  egg-albumin  the  ratio  S  :  N  is 
1  :  8.  The  S  :  N  of  the  urine  in  starvation  is  1  :  15,  but  after 
ingesting  egg-albumin  it  was  found  to  be  1  :  9.8.  This  indi- 
cates a  high  specific  oxidation  of  sulphur,  and  leaves  a  residuum 
of  amino-acids  suitable  for  regrouping  into  a  pabulum  of  "de- 
posit protein"  which  is  poor  in  sulphur.  It  remains  to  be 
shown,  however,  whether  such  "deposit  protein"  if  metabolized 
during  the  early  days  of  fasting  will  give  indication  of  a  low 
sulphur  content. 

1  Mendel  and  Lewis:   "Journal  of  Biological  Chemistry,"  1913-14,  xvi,  75. 

2  Cathcart  and  Green:    "Biochemical  Journal,"  1913,  vii,  1. 


170 


SCIENCE    OF   NUTRITION 


Sherman  and  Hawk1  give  curves  showing  beautifully  an 
almost  parallel  elimination  of  sulphur  and  nitrogen  in  man  on  a 
mixed  diet.     A  curve  showing  this  is  here  presented : 


8     DAY 


240 


20Q 


Fig.  13. — The  curves  here  shown  represent  the  relative  fluctuations  in  the 
average  rates  of  excretion  of  nitrogen  and  S03.  The  values  on  the  left  repre- 
sent percentages  of  an  assumed  standard  rate  of  excretion  for  each  of  these  con- 
stituents. It  will  be  seen  that  in  general  the  excretion  of  sulphates  ran  quite 
closely  parallel  to  that  of  nitrogen. 


Wolf2  presents  similar  curves  after  giving  veal  cutlets  or 
casein  to  a  man.  It  is  evident  that  the  early  elimination  of 
sulphur  does  not  always  appear.  Wolf  also  describes  experi- 
ments in  which  after  the  ingestion  of  a  liter  of  raw  white  of  egg 
by  a  man  the  maximal  elimination  of  urinary  sulphur  followed 
that  of  urea  by  several  hours.  In  this  instance  the  ingesta 
contained  16.6  grams  of  nitrogen,  and  the  urine  during  twenty- 
four  hours  only  8.7  grams.  This  indicates  that  a  large  fraction 
of  the  protein  had  a  fate  which  is  purely  speculative. 

If  we  pass  from  the  consideration  of  protein  metabolism,  as 
indicated  by  the  nitrogen  curve,  to  the  consideration  of  the 
intermediary  metabolism  of  protein  we  can  see  more  clearly 
that  the  curve  of  protein  nitrogen  excretion  is  not  a  true  index 
to  the  sum  of  the  activities  contributed  to  the  cells  by  protein 
metabolism. 

1  Sherman  and  Hawk:   "  Amer.  Jour,  of  Physiology,"  1900,  iv,  43. 

2  Wolf:   " Biochemische  Zeitschrift,"  1912,  xl,  193,  234. 


CHAPTER  VI 

THE    INFLUENCE    OF    PROTEIN    FOOD    (Continued) 
PART   II— THE    INTERMEDIARY    METABOLISM 

The  term  "intermediary  metabolism"  with  which  so  much 
modern  work  is  intimately  associated  was  used  by  Bidder  and 
Schmidt  on  the  first  page  of  their  celebrated  "Verdauungssafte 
und  Stoffwechsel,"  published  in  1852.  Their  conception  of 
the  breakdown  of  protein  has  already  been  cited. 

Voit1  believed  that  there  was  an  early  cleavage  of  the  pro- 
tein molecule  into  a  nitrogenous  portion  and  a  non-nitrogenous 
portion,  a  cleavage  involving  the  liberation  of  only  a  small 
amount  of  energy;  that  there  was  a  rapid  combustion  of  the 
nitrogenous  radicle,  as  shown  by  the  elimination  of  the  nitrog- 
enous end-products  in  the  urine ;  and  that  the  non-nitrogenous 
radicle  which  contained  the  major  part  of  the  potential  energy 
of  the  protein  molecule  might  in  part  be  temporatily  stored 
either  as  glycogen  or  fat  and  be  gradually  doled  out  to  the 
tissues  as  the  need  required. 

Claude  Bernard  believed  that  glycogen  could  arise  from 
protein.  Wolffberg2  let  fowls  fast  two  days  to  remove  the  gly- 
cogen and  then  for  two  days  gave  meat  powder  which  was 
free  from  carbohydrate.  Two  fowls,  killed  during  the  inter- 
val of  protein  digestion,  showed  considerable  glycogen  in 
their  livers  (1.56' and  1.45  per  cent.)  and  muscles  (0.251  and 
0.454  per  cent.),  much  more  than  would  have  been  present  in 
starvation.  Two  similar  fowls,  killed  seventeen  and  twenty- 
four  hours  after  the  last  protein  ingestion,  contained  much  less 
glycogen  in  their  livers  (0.145  and  0.22  per  cent.)  and  muscles 
(0.21 1  and  0.162  per  cent.).  This  origin  of  glycogen  from  pro- 
tein was  fully  confirmed  by  Kiilz3  in  a  very  extended  series  of 

1  Voit:   "Zeitschrift  ftir  Biologie,"  1891,  xxviii,  291. 

2  Wolffberg:   Ibid.,  1876,  xii,  278. 

3  Kiilz:   "Ludwig's  Festschrift,"  1890,  p.  83. 

171 


172  SCIENCE    OF   NUTRITION 

experiments  in  which  chopped  meat,  fully  extracted  with  warm 
water,  was  made  the  basis  of  the  ingesta.  It  became  evident 
from  these  experiments  that  if  sufficient  protein  were  given  to 
an  animal,  part  of  the  protein  carbon  could  be  retained  as 
glycogen. 

It  has  long  been  believed  that  sugar  arises  from  protein  in 
diabetes.  Kossel,1  who  knew  that  hexone  bases,  leucin,  and 
other  protein  end-products  contained  six  atoms  of  carbon,  first 
suggested  a  relation  between  them  and  glucose.  The  theory 
of  the  origin  of  sugar  in  diabetes  from  these  amino  products 
was  strongly  advocated  by  Friedrich  Miiller.2  The  definite 
proof  of  this  was  afforded  by  Stiles  and  Lusk,3  who  gave  a 
mixture  of  amino  bodies  prepared  by  the  pancreatic  proteolysis 
of  meat  to  a  dog  rendered  diabetic  with  phlorhizin.  The 
mixture  was  free  from  protein.  The  nitrogen  ingested  was 
entirely  eliminated  in  the  urine,  and  for  each  gram  of  such 
nitrogen  2.4  grams  of  extra  sugar  appeared  in  the  urine. 

Considerable  sugar  may  originate  from  protein  in  the  course 
of  its  ordinary  metabolism.  The  question  arises  at  what 
time  during  the  metabolism  does  this  sugar  become  avail- 
able for  combustion  in  the  organism?  This  question  was 
answered  by  an  experiment  of  Reilly,  Nolan,  and  Lusk.4 
These  authors  gave  a  fasting  phlorhizinized  dog  500  grams  of 
meat  and  collected  the  urine  in  two  three-hour  and  one 
six-hour  periods.     The  results  were  as  follows: 

EXCRETION     OF     GLUCOSE     AND     NITROGEN     BEFORE     AND 
AFTER    INGESTING    500   GRAMS    OF   MEAT    IN    DIABETES 

Glucose.  Nitrogen.  D  :  N. 

Preceding  three  hours 5.96  1.75  3.41 

First  three  hours  after  feeding 12.43  2.52  4.92 

Second  three  hours  after  feeding 14-7°  3-76  3.91 

Third  three  hours  after  feeding 11-23  3.85  2.92 

Fourth  three  hours  after  feeding 11.23  3-^5  2.92 

Following  three  hours 6.34  1.78  3.56 

1  Kossel:    "Deutsche  medizinische  Wochenschrift,"  1898,  xxiv,  581. 

2  Miiller  and  Seemann:   Ibid.,  1899,  xxv,  209. 

3  Stiles  and  Lusk:    "American  Journal  of  Physiology,"  1903,  ix,  380. 

4  Reilly,  Nolan,  and  Lusk:  "American  Journal  of  Physiology,"  1898,  i,  395. 
For  similar  work  after  giving  casein,  serum  albumin,  gliadin,  and  edestin  with 
separation  of  urine  in  hourly  periods,  consult  Janney:  "Journal  of  Biological 
Chemistry,"  1915,  xx,  321. 


THE  INFLUENCE  OF  PROTEIN  FOOD  1 73 

The  normal  fasting  relation  between  glucose  and  nitrogen 
changed  immediately  upon  the  ingestion  of  meat.  During  the 
first  hours  more  glucose  was  eliminated  than  corresponded 
to  the  nitrogen  in  the  urine.  During  the  later  hours  this 
proportion  was  reversed.  The  sugar  elimination,  therefore, 
took  place  decidedly  before  that  of  the  nitrogen.  This  is 
shown  in  the  following  calculation  of  the  percentage  elimination 
of  nitrogen  and  glucose  in  three-hour  periods  following  the 
ingestion  of  500  grams  of  meat  in  the  above  experiment : 

Glucose.  Nitrogen. 

During  first  three  hours 25.06  18.02 

During  second  three  hours 29.64  26.90 

During  third  three  hours 22.65  27-54 

During  fourth  three  hours 22.65  27.54 

100.00  100.00 

The  relations  are  represented  in  the  following  curve: 


6trams  MforJhrJ 
4~ 


1 

s'z> 

(\ 

\  \ 

I  / 

\  \ 

1   / 

\\ 

\\ 

\ 

grants  D. for  Jhrc 
10- 6 

71 
3S 


u6  * 

Hours. 


IZ 


■  Nitrogen,. 
OexCrose. 


Fig.  14. — Curve  showing  the  elimination  of  glucose  before  nitrogen  after  meat 
ingestion  (500  grams)  in  diabetes. 


That  the  glucose  production  from  the  meat  ingested  was 
proportional  to  the  protein  destroyed  is  evident  from  the  fol- 
lowing comparison,  in  which  the  sum  of  the  glucose  and  nitro- 
gen eliminated  in  the  twelve  hours  is  considered.     Nitrogen 


174  SCIENCE   OF   NUTRITION 

and  glucose  double  in  quantity  after  the  ingestion  of  meat, 
but  their  ratio  remains  the  same  as  in  starvation. 

Glucose.  Nitrogen.  D  :  N. 

Fasting  twelve  hours 23.87  7.00  3.41 

After  500  gm.  meat,  twelve  hours 49-59  14.00  3.54 

Subsequent  twelve  hours 25.36  7.1 1  3.56 

The  curve  shows  that  there  is  an  early  production  of  sugar 
from  protein  which  may  be  liberated  in  metabolism  before  the 
nitrogen  belonging  to  the  protein  is  eliminated  in  the  urine.  A 
similar  early  production  of  sugar  from  protein  has  also  been 
observed  after  feeding  dogs  with  meat  in  pancreas  diabetes.1 

Since  1  gram  of  nitrogen  in  the  urine  represents  a  destruc- 
tion of  6.25  grams  of  meat  protein,  and  since  there  is  simultane- 
ously an  average  elimination  of  3.65  grams  of  glucose  in  phlor- 
hizin  diabetes,  it  may  be  calculated  that  the  sugar  production 
from  meat  amounts  to  58  per  cent,  by  weight  of  the  meat  pro- 
tein metabolized  and  may  contain  51  per  cent,  of  its  total 
available  energy  (see  p.  471). 

Another  calculation  shows  that  of  the  carbon  from  protein 
which  is  ordinarily  eliminated  in  the  respiration  57.2  per  cent, 
may  pass  through  the  glucose  stage  (see  p.  470). 

After  the  ingestion  of  protein  in  the  normal  organism  this 
sugar  early  becomes  available  and  may  be  oxidized  before  the 
nitrogen  belonging  to  it  is  eliminated,  or  if  the  sugar  be  formed 
in  excess,  it  may  be  stored  as  glycogen  in  the  liver  and  muscles 
of  the  body  for  subsequent  use.  In  this  way  it  is  obvious  that 
at  least  half  the  energy  in  protein  may  be  independent  of  the 
curve  of  nitrogen  elimination,  but  may  rather  act  as  though  it 
had  been  ingested  in  the  form  of  carbohydrate.  This  will  be 
explained  in  the  next  chapter.  It  is  therefore  evident  that 
this  carbohydrate,  which  is  early  supplied  in  the  breaking 
down  of  protein,  may  distribute  its  energy  according  to  the 
requirement  of  the  cells  as  long  as  it  lasts.  This  is  apparently 
the  principal  cause  of  the  comparative  evenness  of  the  carbon 

Merger:  Inaugural  Dissertation,  Halle  (Nebelthau),  1901;  cited  from 
Maly's  "  Jahresbericht  iiber  Thierchemie,"  xxxi,  848. 


THE   INFLUENCE    OF   PROTEIN   FOOD  175 

dioxid  excretion  as  contrasted  with  the  great  irregularity  of  the 
nitrogen  elimination  after  protein  ingestion. 

Pfiiiger  who,  longer  than  any  physiologist,  denied  the 
validity  of  any  existing  proof  that  glucose  arose  from  protein, 
was  in  his  old  age  ultimately  convinced  by  the  following 
experiments.  He1  found  that  when  dogs  were  allowed  to 
fast  for  ten  days  and  then  made  diabetic  by  an  injection  of 
phlorhizin  the  glycogen  of  the  liver  amounted  to  o.i  per  cent, 
and  of  the  muscles  to  0.2  per  cent.  If  dogs  reduced  to  this  con- 
dition were  given  large  quantities  of  codfish  (which  contains 
only  0.03  per  cent,  glycogen)  the  glycogen  content  of  the  liver 
averaged  6.5  per  cent.,  and  in  one  case  rose  to  9.9  per  cent., 
and  the  glycogen  content  of  the  muscle  averaged  1  per 
cent.  Since  fat  ingestion  was  without  effect  upon  the  gly- 
cogen store,  Pfiiiger  acknowledged  the  origin  of  glucose  from 
protein. 

It  must  be  borne  in  mind  that  it  is  not  very  long  ago  that 
it  was  perfectly  permissible  to  think  of  protein  as  a  complex 
containing  many  glucose  molecules  existing  in  a  highly  poly- 
merized condition  and  combined  with  nitrogen-containing 
radicles,  of  which  glycocoll,  leucin,  and  tyrosin  at  least  were 
readily  obtainable  as  cleavage  products.  Such  a  molecule 
explained  the  older  conceptions  of  protein  metabolism.  The 
work  of  Hofmeister,  Kossel,  and  Emil  Fischer  first  gave  a 
true  insight  into  the  composition  of  the  protein  molecule. 
One  must  know  the  life  history  of  sixteen  amino-acids 
in  order  to  be  familiar  with  the  metabolism  of  protein. 
Though  the  extension  of  knowledge  may  have  been  at  the 
cost  of  simplicity,  yet  order  is  being  wrought  out  of  apparent 
complexity.  It  is  often  difficult  for  an  older  generation  to 
think  in  terms  of  the  knowledge  of  a  new.  The  author's 
father  was  a  student  at  Heidelberg  at  the  time  when  the  mod- 
ern chemical  formulae  were  introduced,  when  H — O  became 
H20,  and  he  recalled  the  distracted  exclamation  of  one  of  the 
university  professors,  "Ach  Gott!  wie  kann  man  so  lernen!" 

1  Pfiiiger  and  Junkersdorf:    "Pfluger's  Archiv,"  1910,  cxxxi,  201. 


176  SCIENCE   OF   NUTRITION 

The  intimate  knowledge  of  the  behavior  of  the  amino- 
acids  within  the  body  may  be  studied  by  a  variety  of 
means. 

1 .  The  direct  removal  in  the  urine  of  certain  of  the  amino- 
acids,  such  as  glycocoll  and  cy stein,  or  the  removal  of  slightly 
changed  products,  such  as  homogentisic  acid  from  tyrosin 
and  kynurenic  acid  from  tryptophan. 

2.  The  determination  in  the  urine  of  a  dog  made  diabetic 
by  phlorhizin  of  the  quantity  of  "extra  glucose"  eliminated 
after  the  ingestion  of  certain  amino-acids,  and  the  determina- 
tion of  an  increase  in  the  quantity  of  /3-oxybutyric  acid  after 
the  administration  of  other  amino-acids  under  like  conditions. 

3.  The  results  of  experiments  in  which  an  amino-acid  is 
added  to  warmed  oxygenated  blood  and  this  perfused  through 
a  surviving  liver,  subsequent  analysis  of  the  blood  revealing 
any  chemical  change  which  the  material  might  have  under- 
gone. 

It  should  be  remembered  that  when  amino-acids  are  in- 
gested the  resulting  nitrogen  increase  in  the  urine  is  entirely 
due  to  urea.1  The  same  is  true  of  the  dipeptid  glycyl-glycin2 
(see  p.  75).  It  is  believed  that  the  deamination  of  an  amino- 
acid  results  in  the  formation  of  ammonia,  which,  becoming 
ammonium  carbonate,  may  be  converted  into  urea.  Yet 
experiments  in  vitro  have  failed  to  demonstrate  this  action. 
Gertrude  Bostock3  found  that  the  liver  and  intestinal  mucosa 
failed  to  deaminize  alanin.  Levene  and  Meyer4  find  that 
leukocytes  and  kidney  tissue  do  not  deaminize  glycocoll, 
alanin,  aspartic  acid,  and  leucin.  Griesbach  and  Oppen- 
heimer5  are  of  the  same  opinion.  Thus  the  characteristic 
biologic  reaction  of  deamination  is  effected  through  the  activity 
of  living  tissue  cells.     Special  enzymes  are  nowhere  in  evidence. 

For  the  understanding  of  the  biochemic  relations  of  the 

1  Levene  and  Kober:    "American  Journal  of  Physiology,"  1909,  xxiii,  324. 

2  Levene  and  Meyer:    Ibid.,  1909-10,  xxv,  214. 

3  Bostock:    "Biochemical  Journal,"  1911,  vi,  48. 

4  Levene  and  Meyer:  "Journal  of  Biological  Chemistry,"  1913,  xv,  65; 
1913-14,  xvi,  555. 

5  Griesbach  and  Oppenheimer:    "  Biochemische  Zeitschrift,"  1913,  Iv,  329. 


THE  INFLUENCE  OF  PROTEIN  FOOD  1 77 

various  amino-acids  it  seems  desirable  to  present  as  briefly  as 
possible  the  laws  governing  their  fate  in  the  organism.1 

THE   PROCESS    OF   DEAMINATION 

The  nature  of  the  attack  of  the  living  cell  upon  the  NH2 
group  of  the  amino-acids  has  been  the  subject  of  much  in- 
vestigation. The  process  was  at  first  thought  to  be  one  of 
simple  hydrolysis,  as  follows: 

R-CHNH2-COOH  +  HOH  =  R-CHOH-COOH  +  NH3 

After  this  fashion  glycocoll,  CH2NH2 — COOH,  would  become 
glycollic  acid,  CH2OH— COOH;  alanin,  CH3— CHNH2— 
COOH,  would  become  lactic  acid,  CH3— CHOH— COOH, 
and  so  forth. 

It  was  Otto  Neubauer,2  in  the  laboratories  of  the  second 
medical  clinic  of  the  University  of  Munich,  who  first  showed 
that  the  process  of  deamination  might  be  one  of  oxidation  and 
not  hydrolysis.  This  process  of  oxidative  deamination  is 
represented  in  the  following  formula: 

R-CHNH2-COOH  +  O  =  R-CO-COOH  +  NH3 

From  glycocoll,  CH2NH2— COOH,  one  would  thus  obtain  gly- 
oxylic  acid,  CHO— COOH;  and  from  alanin,  CH3— CHNH2— 
COOH,  pyruvic  acid,  CH3— CO— COOH. 

That  this  method  of  oxidation  is  actually  possible  in  the 
organism  was  evident  when  Neubauer  gave  phenyl-glycocoll  to 
a  dog  and  found  phenyl-glyoxylic  acid  as  well  as  mandelic  acid 
in  the  urine. 

CeH6  CeHs  CeH6 

I  I  I 

CHNH2  ►  CO  CHOH 

I  I  I 

COOH  COOH  COOH 

Phenyl-glycocoll.  Phenyl-glyoxylic  acid.  Mandelic  acid. 

1  For  excellent  reviews,  see  Dakin:  "Oxidations  and  Reductions  in  the 
Animal  Body,"  Longmans,  Green  and  Co.,  191 2;  Underhill,  "The  Physiology 
of  the  Amino-Acids,"  Yale  University  Press,  1915. 

2  Neubauer:    "Deutsches  Archiv  fiir  klinische  Medizin,"  1909,  xcv,  211. 


1 78 


SCIENCE   OF   NUTRITION 


Further  evidence  was  obtained  by  Neubauer  through  the 
medium  of  a  rare  anomaly  of  human  metabolism  called 
alcaptonuria  (see  p.  196).  In  this  disease  ty rosin  and  phenyl- 
alanin  are  not  oxidized  to  their  usual  end-products,  but  are 
eliminated  in  the  urine  as  homogentisic  acid.  The  trans- 
formation of  phenyl-alanin  and  tyrosin  into  homogentisic 
acid  is  believed  to  follow  the  scheme  presented  below: 


OH 


OH 


/\ 


IOH 


OH 


OH 


IOH 


CH2 
CHNH2 


CH2 
CO 


HO      CH2 
CO 


CH2 
CO 


CH2 

COOH 

Homogentisic  acid. 


COOH  COOH  COOH  COOH 

Tyrosin.         p-Oxyphenyl-pyruvic        Quinoid    inter-      Hydroquinone 
acid.  mediary  prod-       pyruvic  acid. 

I  uct      (hypo- 

thetical). 


CH2 

CHNH2 
I 
COOH 

Phenyl-alanin. 


It  will  be  noted  that  the  alanin  radicle,  CH2 — CHNH2 — 
COOH,  is  represented  as  undergoing  oxidative  deamination, 
being  converted  into  pyruvic  acid.  Neubauer  drew  this 
conclusion  from  the  fact  that  if  phenyl-alanin,  tyrosin,  or 
p-oxy-phenyl-pyruvic  acid  were  given  to  the  alkaptonuric 
patient  they  all  appeared  in  the  urine  as  homogentisic  acid, 
whereas  when  p-oxy-phenyl-lactic  acid  was  given  there  was  no 
increase  in  the  homogentisic  acid  excretion  whatever.  Con- 
sequently it  could  not  have  been  an  intermediary  product  in 
the  metabolism  of  tyrosin.  Neubauer,  therefore,  concluded 
that  the  primary  pathway  of  deamination  was  oxidative  and 


THE    INFLUENCE    OF   PROTEIN   FOOD 


179 


not  hydrolytic.    Later  he1  presented  the  following  formula  as 
indicating  the  probable  reaction  of  oxidative  deamination : 


C6H5 

H 

C  +     O 

|\ 

NH2 
COOH 

Amino-acid. 


C6H5 
I      OH 

1/ 
C 

|\ 

NH2 
COOH 

Oxy-amino-acid . 


CeHs 

CO  +    NH3 


COOH 

Keto-acid. 


Alanin,  for  example,  would  follow  this  pathway: 


CH3 
H 

1/ 

c        +   o 

f\ 

NH2 
COOH 

Alanin. 


CH3 


OH 


CH3 

CO  +     NH3 


C  

|\ 

NH2 
COOH  COOH 

Oxy-amino-propionic  acid.  Pyruvic  acid. 


Examination  of  the  formula  given  for  the  conversion  of 
phenyl-alanin  into  homogentisic  acid  shows  that  the  alanin 
radicle  of  phenyl-alanin  is  converted  into  an  acetic  acid  radicle 
in  homogentisic  acid.  The  question  arises  whether  the  first 
step  in  the  destruction  of  phenyl-alanin  might  not  be  the  loss 
of  its  acid  group  by  C02  cleavage,  as  indeed  happens  when  it 
is  acted  upon  by  bacteria,2  and  as  is  usual  in  the  transformation 
of  cy stein  into  taurin. 


C6H5 

CeHs 

CH2SH 

CH2S03H 

CH2 

>        CH2 

CHNH2        - 

-+        CH2NH2 

CHNH2 

1 
COOH 

lenyl-alanin. 

CH2NH2 
CO, 

Phenyi-ethyl-amin. 

COOH 

Cystein. 

C02 

Taurin. 

As  phenyl-ethyl-amin  is  poisonous,  its  first  oxidation  prod- 
uct, phenyl-ethyl-alcohol,  was  given  by  Neubauer  to  the  al- 
kaptonuria but  without  increasing  the  quantity  of  homogen- 
tisic acid.     It  appeared  in  the  urine  as  phenyl-acetic  acid 

1  Neubauer  and  Fromherz:  "Zeitschrift  fur  physiologische  Chemie,"  1910, 
lxx,  326. 

2Spiro:    "Hofmeister's  Beitrage,"  1902,  i,  347. 


l8o  SCIENCE    OF   NUTRITION 

(paired  with  glycocoll).  This  indicates  that  oxidative 
deamination  takes  place  in  the  metabolism  of  phenyl-alanin 
before  C02  is  split  from  the  acid  radicle.  The  C02  cleavage 
follows  deamination,  as  appears  in  the  formula  given  for  the 
transformation  of  hydroquinone-pyruvic  acid  into  homo- 
gentisic  acid.  It  follows  from  this  that  after  the  oxidative 
deamination  of  an  amino-acid,  the  deaminized  remainder  may 
be  converted  into  an  acid  containing  one  less  carbon  atom,  as 
follows : 

R  R  R  R 

I  II  I 

CH2  CH2  CH2  CH2 

I  II  I 

CHNH2     +     0  CO  CHO     +     O  COOH 

I  I 

COOH  COOH        C02 

If  after  producing  the  aldehyde  by  C02  cleavage,  reduction 
prevails  instead  of  oxidation,  then  an  alcohol  is  formed  in- 
stead of  an  acid.  This  may  be  illustrated  by  the  work  of  F. 
Ehrlich,1  who  found  that  when  yeast  acted  on  tyrosin  the  end- 
product  was  p-oxy-phenyl-ethyl-alcohol,  OH — C6H4 — CH2- 
CH2OH.  Neubauer  and  Fromherz,  continuing  their  theo- 
retic researches,  discovered  that  yeast  acting  on  p-oxy-phenyl- 
pyruvic  acid  yields  this  same  ethyl-alcohol  derivative,  while 
p-oxy-phenyl-lactic  acid  does  not  give  it.  Para-oxy-phenyl- 
pyruvic  acid  may,  therefore,  be  transformed  as  follows: 

C6H5OH 

I 
CH2 

I 
CH,OH 

p-Oxy-phenyl-ethyl-alcohol. 


Although  p-oxy-phenyl-lactic  acid  is  not  acted  on  by  yeast, 
yet  it  also  appears  as  a  product  when  yeast  acts  on  p-oxy- 
phenyl-pyruvic  acid.  Hence  pyruvic  acid  may  be  reduced, 
with  the  formation  of  lactic  acid. 

1  Ehrlich,  F.:   "Ber.  d.  d.  chem.  Ges.,"  1907,  xl,  1047. 


C6H5OH 

C6H5OH 

CH2 

1 

CH2 

CO 

CHO          + 

COOH 

C02 

p-Oxy-phenyl-acetaldehyd, 

THE  INFLUENCE  OF  PROTEIN  FOOD  l8l 

CeHjOH  C6H6OH 

I  I 

CH2  CH2 

I  I 

CO  +     H2  =  CHOH 

I  I 

COOH  COOH 

In  conformity  with  this  stands  the  observation  of  P. 
Mayer,1  who  found  that  if  pyruvic  acid  were  administered  to  a 
rabbit  lactic  acid  appeared  in  the  urine. 

Although  it  appears  certain  that  oxidative  deamination  is 
the  principal  method  of  attack  upon  the  amino  group  of  the 
aromatic  acids,  yet  direct  hydrolytic  deamination  has  been 
noted  for  them,  and  it  may  play  a  considerable  role  in  the 
metabolism  of  the  amino-acids  of  the  aliphatic  series  as  well. 
Neubauer  finds  the  laevo-component  of  p-oxy-phenyl-lactic 
acid  in  the  urine  of  a  patient  suffering  from  cirrhosis  of  the 
liver.  Since  the  dextro-component  is  always  eliminated  in  the 
human  being  whenever  it  is  formed  by  reduction  of  p-oxy- 
phenyl-pyruvic  acid  within  the  organism,  it  follows  that  this 
latter  substance  could  not  have  been  the  intermediary  one, 
but  that  the  1-compound  was  formed  by  the  direct  hydrolytic 
cleavage  of  1-ty rosin. 

These  reactions  give  one  an  insight  into  oxidations, 
reductions,  hydrolyses,  and  cleavages,  which  are  of  constant 
occurrence  as  the  result  of  vital  activities.  One  may  sum- 
marize all  these  possible  biologic  variations  in  the  following 
scheme,  using  alanin  as  a  typical  amino-acid: 

♦0  CH_ 

I 

COOH 
acetic  acid 
♦H2     CH3 

I 

CHaOH 
ethyl  alcohol 


I 

COOH 
lactic  add 

1  Mayer,  P.:    "Biochemische  Zeitschrift,"  1912,  xl,  441. 


CH           CH   y^ 
3            H3  X 

T*y 

0 

•               1 

C      >   CHO  N\^ 

j         acetaldehyde 

\ 

CHNH2 

CO. 

COOH 

1     \ 
COOH  ^ 
alanin 

+HOH 

pyruvic  acid 

— » 

CHOH 

1 82  SCIENCE   OF   NUTRITION 

It  has  been  noted  by  Kotake1  that  although  p-oxy -phenyl- 
pyruvic  acid  is  completely  oxidized  when  administered  to  a 
rabbit,  p-oxy-phenyl-lactic  acid  remains  almost  untouched  and 
appears  in  the  urine.  The  fact,  however,  that  lactic  acid  and 
alanin  pass  over  into  sugar  much  more  readily  than  does 
pyruvic  acid  leads  Ringer2  to  believe  that  the  metabolism  of 
alanin  probably  follows  the  path  of  hydrolytic  deamination 
into  lactic  acid  rather  than  that  of  oxidative  deamination  into 
pyruvic  acid. 

The  reader  should  realize  that  there  are  many  possible 
pathways  in  metabolism,  and  the  above  presentation  may  be 
regarded  as  suggestive  rather  than  literally  exact. 

THE   OXIDATION  OF  FATS 

In  order  to  be  able  to  understand  the  further  fate  of  some 
of  the  deaminized  remainders  of  the  amino-acids,  the  method  of 
oxidation  of  fatty  acids  must  be  understood.  The  experi- 
ments of  Knoop3  are  based  on  the  fact  that  benzoic  acid, 
C6H5COOH,  when  given  to  an  animal  pairs  with  glycocoll  and 
appears  as  hippuric  acid  in  the  urine,  whereas  phenylacetic 
acid,  C6H5CH2COOH,  when  given  pairs  in  the  same  way 
and  is  eliminated  as  phenaceturic  acid.  Knoop  found  that 
whenever  aromatic  derivatives  of  the  fatty  acids  were  given 
to  an  animal  one  of  these  two  forms  always  appeared  in  the 
urine;  that  if  the  side  chain  had  an  odd  number  of  carbon 
atoms  hippuric  acid  was  always  the  end-result,  and  if  there 
were  an  even  number  of  atoms  phenaceturic  acid  appeared  as 
the  final  product. 

The  following  substances  were  given: 

C6H5— CH2— CHo— CH2— CH2— COOH     Phenylvalerianic  acid. 
P 

C6H5— CH2— CH2— CH2— COOH     Phenylbutyric  acid. 

ft 

C6H5— CH2— CH2— COOH    Phenylpropionic  acid. 

1  Kotake:    "Zeitschrift  fiir  physiologische  Chemie,"  1010,  lxix,  409. 

2  Ringer:   "Journal  of  Biological  Chemistry,"  1913,  xv,  145. 

3  Knoop:    "Hofmeister's  Beitrage,"  1905,  vi,  150. 


THE  INFLUENCE  OF  PROTEIN  FOOD  183 

Since  phenylvalerianic  and  phenylpropionic  acids  both 
yielded  hippuric  acid  and  phenylbutyric  did  not,  it  was  evident 
that  the  last  named  was  not  an  intermediary  product  between 
the  first  two.  Knoop,  therefore,  concluded  that  in  the  oxida- 
tion of  fats  the  /3-carbon  atom  was  oxidized  and  that  two  car- 
bon atoms  dropped  from  the  chain  together.  This  view  was 
supported  by  Dakin's1  discovery  that  when  phenylpropionic 
acid  was  given  in  large  amounts  phenyl-/3-oxy-propionic  acid, 
C6H5— CHOH— CH2— COOH,  was  detected  in  the  urine. 
Corroborative  evidence  is  further  found  in  the  fact  that  when 
body  fat  or  food  fat,  both  of  which  always  contain  an  even 
number  of  carbon  atoms,  are  metabolized  in  the  diabetic,  the 
end-product  is  always  /3-oxybutyric  acid,  CH3CHOHCH2- 
COOH,  which  one  would  expect  in  terms  of  the  theory. 

It  is  interesting  to  note  the  results  of  giving  the  following 
three  substances: 

CeH5COCH2COOH  >        C6H5COOH 

CeHsCHoCOCOOH  ►        oxidized 

C6H5COCH2CH2COOH        ►        C6H5CH2COOH 

Phenyl-/3-keto-propionic  acid  is  oxidized  on  the  /3-carbon 
atom  to  benzoic  acid.  Phenyl-a-keto-propionic  acid  (phenyl- 
pyruvic  acid),  as  stated,  is  completely  oxidized  in  the  organ- 
ism, while  phenyl-f-keto-butyric  acid  undergoes  reduction  of 
its  T'-carbon  and  oxidation  of  its  /3-carbon  and  is  eliminated  in 
the  urine  as  phenyl-acetic  acid.  Here  reduction  and  oxidation 
play  alternately  upon  the  same  molecule. 

The  oxidation  of  unsaturated  fatty  acids,  or  such  as  have  a 
double  linkage  between  two  carbon  atoms,  follows  the  same  laws 
as  the  oxidation  of  saturated  fatty  acids.  Thus,  Erdmann  and 
Marchand2  found  that  if  cinnamic  acid,  C6H5.CH:CH.COOH, 
be  given  to  an  animal,  benzoic  acid  appears  in  the  urine. 
Dakin3  administered  the  material  in  large  doses  to  cats  and 
found  the  intermediary  oxidation  product,  phenyl-/3-oxy-pro- 
pionic  acid,  C6H5.CHOH.CH2COOH,  in  the  urine. 

1  Dakin:   "Journal  of  Biological  Chemistry,"  1909,  vi,  203. 

2  Erdmann  and  Marchand:   "Liebig's  Annalen,"  1842,  xliv,  344. 

3  Dakin:   "Oxidations  and  Reductions  in  the  Animal  Body,"  1912,  p.  36. 


184  SCIENCE    OF   NUTRITION 

This  preliminary  discussion  has  shown  that  amino-acids 
are  oxidized  at  the  a-position  which  is  the  point  of  attachment 
of  the  NH2  group,  and  are  converted  into  oxy-  or  keto-acids  and 
then  into  acids  having  one  less  carbon  atom.  After  this  the 
organic  acid  becomes  subject  to  the  laws  of  /3-oxidation,  under 
which  a  fatty  acid  is  oxidized  on  its  /3-carbon  atom,  oxy- 
and  keto-acids  being  first  formed,  and  then  there  is  cleavage 
of  two  carbon  atoms  with  the  formation  of  an  acid  which 
contains  two  less  carbon  radicles  than  before.  Frequently 
/3-oxybutyric  acid  is  an  intermediary  product  of  this  oxidation, 
just  as  happens  in  the  case  of  fatty  acids.  In  other  cases  in 
which  the  product  contains  three  atoms  of  carbon,  the  end- 
product  may  be  converted  into  glucose  in  the  organism. 
Ringer1  has  demonstrated  that  in  the  /3-oxidation  of  fatty 
acids  having  uneven  numbers  of  carbon  atoms  sugar  is 
formed  from  them  in  the  diabetic  organism  in  proportion  to 
the  power  to  produce  propionic  acid,  CH3.CH2.COOH.  This 
might  form  /3-lactic  acid,  CH2OH.CH2COOH,  which,  in  turn, 
might  be  converted  into  glucose. 

Experiments  have  shown  that  the  glucose-forming  amino- 
acids  include  glycocoll,  alanin,  prolin,  aspartic  and  glutamic 
acids,  serin,  cystin,  and  arginin.  Some  of  the  other  amino- 
acids  yield  /3-oxybutyric  acid  as  an  intermediary  product. 

It  seems  desirable  at  this  point  to  enter  into  the  more 
intimate  details  of  the  life-history  of  the  different  amino-acids. 
Though  the  general  energy  metabolism  may  be  understood 
without  this  knowledge,  yet  the  finer  comprehension  of  the 
subject  cannot  be  otherwise  obtained. 

THE   FATE    OF    THE   AMINO-ACIDS 

Glycocoll  (CH2NH2.COOH).— Probably  both  carbon  atoms 
are  able  to  enter  into  the  formation  of  glucose.  Present  in  most 
proteins;  in  large  amount  in  gelatin;  absent  in  milk  proteins  and 
in  gliadin  of  wheat. 

It  has  been  noted  that  when  benzoic  acid  is  administered  to 

1  Ringer:   "Journal  of  Biological  Chemistry,"  1013,  xiv,  43. 


THE  INFLUENCE  OF  PROTEIN  FOOD  1 85 

an  animal  it  forms  a  synthetic  compound  with  glycocoll 
within  the  organism  which  is  ehminated  in  the  urine  as  hip- 
puric  acid. 

CeHs-COOH  +  CH2.NH2.COOH  =  C6H5CO.NHCH2.COOH  +  H20. 
Hippuric  acid  is  found  in  the  urine  of  horses  and  cattle  in  the 
food  of  which  materials  convertible  into  benzoates  are  found. 
It  is  eliminated  almost  as  soon  as  it  is  formed,  for  Lewis1  found 
after  administering  hippuric  acid  to  a  man  that  82  per  cent, 
could  be  recovered  in  the  urine  within  three  hours. 

Lewinski2  found  that  when  10  or  20  grams  of  benzoic  acid 
were  administered  to  a  man  in  the  form  of  sodium  benzoate 
the  entire  quantity  of  benzoic  acid  was  combined  and  elimin- 
ated in  the  form  of  hippuric  acid.  Only  when  the  power  to 
form  glycocoll  was  exceeded  was  there  an  ehmination  of 
benzoic  acid.  Thus,  after  giving  50  grams  of  benzoic  acid, 
62.3  grams  of  hippuric  acid  containing  42.3  grams  of  combined 
benzoic  acid  were  ehminated,  together  with  8.2  grams  of 
uncombined  acid. 

The  following  data  are  taken  from  Lewinski's  experiments 
upon  the  same  individual  when  partaking  of  low  and  of  high 
protein  diets.     The  figures  are  for  twenty-four  hours: 


Benzoic  Acid 

Total  N 

Hippuric 

Administered. 

in  Urine. 

Acn>  N. 

HN 

Grams. 

Grams. 

Grams. 

TN 

25 

9-3 

2.74 

29.4 

40 

9.0 

3-15 

34-9 

40 

23-7 

4.06 

18.0 

5° 

29.1 

4.87 

18.6 

When  there  were  9  grams  of  total  nitrogen  eliminated, 
3.15  grams  or  35  per  cent,  appeared  in  the  form  of  glycocoll. 
When  29  grams  of  total  nitrogen,  only  4.87  grams  of  nitrogen 
appeared  in  the  form  of  glycocoll.  In  other  words,  an  increase 
of  20  grams  of  nitrogen  in  the  urine  was  accompanied  by  an 
increase  of  1.72  grams  of  glycocoll  nitrogen,  which  is  only 
8.5  per  cent,  of  the  increase  in  protein  metabolism  instead  of 
35  per  cent. 

1  Lewis:   "Journal  of  Biological  Chemistry,"  1914,  xviii,  225. 
2Lewinski:  "Archiv  fur  ex.  Path,  und  Pharm.,"  1908,  lviii,  397.     See  also 
Dakin:    "Journal  of  Biological  Chemistry,"  1909-10,  vii,  103. 


1 86  SCIENCE   OF   NUTRITION 

Magnus-Levy1  found  that  25  to  27  per  cent,  of  the  total 
urinary  nitrogen  of  rabbits  fed  with  cream  and  of  a  goat  fed 
with  hay  is  excreted  in  the  form  of  hippuric  acid  when  ben- 
zoate  of  soda  is  administered  with  the  food.  He  calculated 
that  only  4  per  cent,  of  this  could  have  been  derived  from 
glycocoll  preformed  in  the  protein  metabolized,  but  that  20 
per  cent,  could  have  originated  from  leucin  did  this  pass 
through  a  glycocoll  stage. 

It  has  already  been  stated  that  the  individual  amino- 
acids  lose  their  nitrogen  as  the  first  step  in  their  metabolism. 
Only  by  the  union  of  its  nitrogen  atom  with  benzoic  acid  is 
glycocoll  spared  this  fate.  One  might  believe  that  other 
amino-acids  might  unite  with  benzoic  acid  in  a  similar  fashion, 
and  then  be  converted  into  hippuric  acid  by  oxidation  of  the 
rest  of  their  carbon  chains.  To  test  this  hypothesis,  Magnus- 
Levy2  administered  subcutaneously  benzoylated  compounds 
of  alanin,  valin,  leucin,  phenylalanin,  aspartic  acid,  glutamic 
acid,  ornithin,  and  serin.  He  found  that  these  compounds 
were  not  changed  into  hippuric  acid  in  the  organism,  but  were 
eliminated  unchanged  in  the  urine. 

These  experiments  were  a  further  demonstration  that  in 
the  breaking  down  of  amino-acids  deamination  is  the  first 
step,  and  they  leave  no  conclusion  open  other  than  that 
glycocoll  arises  by  a  synthetic  process. 

The  nature  of  the  process  is  still  a  riddle.  The  great  elimina- 
tion of  glycocoll  in  hippuric  acid  has  been  repeatedly  observed 
by  Wiechowski3  and  by  Ringer,4  the  latter  finding  that  38 
per  cent,  of  the  total  nitrogen  may  be  eliminated  as  hippuric- 
acid  nitrogen  in  the  fasting  goat.  Parker  and  Lusk5  suggested 
the  synthetic  origin  of  glycocoll,  but  reported  that  carbohy- 
drates had  no  influence  on  the  excretion  of  hippuric  acid. 
Abderhalden  and  Strauss6  gave  a  pig  which  was  nourished 

1  Magnus-Levy:  "Munchenermedizinische  Wochenschrift,"  1905,  lii,  2168. 

2  Magnus-Levy:   "Biochemische  Zeitschrift,"  1907,  vi,  541. 

3  Wiechowski :    "  Hofmeister's  Beitrage,"  1906,  vii,  204. 

4  Ringer:   "Journal  of  Biological  Chemistry,"  1911,  x,  327. 

5  Parker  and  Lusk:   "  Amer.  Jour,  of  Physiology,"  1899-1900,  iii,  472. 

6  Abderhalden  and  Strauss:  "Zeitschrift  fiir  physiologische  Chemie,"  1914, 
xci,  81. 


THE  INFLUENCE  OF  PROTEIN  FOOD 


l87 


on  bran  and  potatoes  12  grams  of  sodium  benzoate  daily,  and 
during  certain  periods  added  glycocoll,  alanin,  and  ammonium 
carbonate.     The  results  were  as  follows: 


Period. 

No.  of  Days. 

Added  to  Food. 

Hippuric  Aero  in 
Urine  24  Hours. 

V 

VI 

VII 

8 
8 
6 

Glycocoll,  12  g. 

2-54 
4-5i 
3-3° 

VIII 
IX 

12 
6 

Alanin,  12  g. 

3-30 
2.63 

X 

18 

Ammonium  carbonate,  15.6  g. 

2.20 

From  this  it  appears  that  glycocoll  when  given  with  the 
benzoate  is  far  from  being  completely  removed  in  the  urine,  and 
that  neither  alanin  which  yields  ammonia  on  deamination  nor 
ammonium  carbonate  itself  have  any  effect  whatever  on  the 
elimination  of  glycocoll. 

McCollum  and  Hoagland1  have  reported  some  remarkable 
experiments.  A  pig,  weighing  46.7  kilograms,  was  brought 
into  a  condition  of  minimal  nitrogen  metabolism  by  giving 
a  diet  of  starch  containing  75  calories  for  each  kilogram  of 
body  weight.  The  diet  was  then  continued  and  increasing 
amounts  of  benzoic  acid  were  added.  Finally,  hydrochloric 
acid  and  benzoic  acid  were  given  together.  The  results  of 
the  urinary  analyses  are  here  reproduced : 


Period. 

No.  of 
Days. 

Food. 

Total 

N. 

IJREA 

N. 

NRVN. 

Creat- 

ININ 

N. 

Other 

N.* 

I 

12 

Starch,    75    cal.    per    kg. 

alk.  salts. 

2.56 

1-43 

0.21 

O.488 

O.424 

II 

4 

Same  4-  4  g.  benzoic  acid. 

2.63 

1.29 

0.21 

O.456 

0.681 

III 

7 

Same  4-  10  g.  benzoic  acid. 

2.23 

0.58 

0.22 

0.484 

O.948 

IV 

5 

Same  4-  16  g.  benzoic  acid. 

2.86 

°-55 

0.3S 

Q-437 

I.492 

V 

5 

Starch  same,  neut.  salts  4- 
16  g.  benzoic  acid  +  io 
g.  25  per  cent.  HC1. 

4-03 

0.54 

1.44 

0.424 

I.632 

*  This  includes  hippuric  acid. 

1  McCollum  and  Hoagland:    "Journal  of  Biological  Chemistry,"  1913-14, 
xvi,  299.     See  also  Lewis:   Ibid.,  1914,  xviii,  225. 


1 88  SCIENCE   OF   NUTRITION 

It  is  evident  from  this  that  when  the  protein  metabolism 
is  reduced  to  a  minimal  level  by  carbohydrate  ingestion 
(see  p.  273)  the  addition  of  benzoic  acid  does  not  affect  the 
creatinin  output,  scarcely  affects  the  total  nitrogen  elimination, 
but  may  reduce  the  total  elimination  of  urea  nitrogen  from 
56  per  cent,  of  the  total  nitrogen  output  to  19  per  cent,  of 
the  total.  This  difference,  or  37  per  cent.,  of  the  total  nitrogen 
which  is  ordinarily  converted  into  urea  is  under  these  circum- 
stances eliminated  as  glycocoll.  It  is  of  great  significance  that 
this  is  accomplished  without  materially  changing  the  amount 
of  protein  metabolism  (see  p.  286).  Giving  hydrochloric  acid 
with  benzoic  acid  greatly  increases  ammonia  formation,  but 
scarcely  influences  the  other  urinary  constituents  (see  p.  219). 
The  urea  elimination  remains  at  its  former  minimal  level. 

This  discussion  has  shown  that  one  may  compute  that  35, 
37,  and  38  per  cent,  of  the  total  endogenous  protein  metabolism 
of  man,  goat,  and  pig  may  pass  through  a  glycocoll  stage  and 
be  eliminated  in  the  urine.  It  is  certain  that  no  protein  con- 
tains this  quantity  of  glycocoll.  In  spite  of  all  the  work 
accomplished  there  is  no  solution  of  the  problem  from  what 
materials  this  synthetic  production  of  glycocoll  occurs.  It 
arises  as  does  creatinin  without  having  as  yet  betrayed  the 
secret  of  its  origin.  The  synthetic  production  of  glycocoll  is 
of  undoubted  value  in  making  possible  the  development  of 
body  tissue  which  contains  glycocoll  from  milk  proteins  which 
are  free  from  it. 

Glycocoll  forms  sugar  in  the  organism.  Ringer  and  Lusk1 
found  that  it  was  completely  converted  into  glucose  in  the 
phlorhizinized  dog. 

The  method  employed  is  to  give  to  a  dog,  rendered  diabetic 
by  phlorhizin  and  then  almost  glycogen  free  by  shivering,  the 
material  to  be  tested,  and  to  observe  the  increased  output  of 
glucose  in  the  urine.  One  may  give  glucose  itself  and  witness 
its  complete  elimination,2  as  follows: 

1  Ringer  and  Lusk:  "Zeitschrift  fur  physiologische  Chemie,"  1010,  lxvi,  106. 

2  Taken  from  Csonka:  "Journal  of  Biological  Chemistry,"  1915,  xx,  543. 


THE    INFLUENCE    OF   PROTEIN   FOOD 


189 


Period.                      Glucose. 

Nitrogen. 

D  :N. 

Extra 
Glucose. 

Preliminary 

Glucose,  16  g 

After  period 

25.92 

2.87 

3.68 
9.00 
3-54 

15-43 

There  were  2.87  grams  of  nitrogen  in  the  urine  of  seven 
hours.  Assuming  the  customary  D:N  =  3.65  :  1  (see  p.  174), 
then  the  quantity  of  glucose  derived  from  the  metabolism 
of  protein  during  the  seven  hours  would  be  2.87  X  3.65  = 
10.49  grams.  Deducting  10.49  grams  from  25.92  grams  found 
in  the  urine,  it  appears  that  15.43  grams  of  extra  sugar  were 
eliminated  during  the  period  of  experimentation. 

In  the  case  of  glycocoll  the  results  may  be  thus  analyzed: 


Period 

Glucose. 

Nitrogen. 

D  :N. 

Extra 
Glucose. 

Preliminary 

Glycocoll,  20  g 

After  period 

47-42 

14.84 

3 -40 
3.20 
3-37 

16.63 

During  a  period  of  fourteen  hours  following  the  ingestion 
of  20  grams  of  glycocoll  containing  3.73  grams  of  nitrogen  14.84 
grams  of  nitrogen  appeared  in  the  urine.  The  difference  or 
9. 1 1  grams  represents  the  nitrogen  of  the  protein  metabolism. 
Multiplying  this  by  the  prevailing  D  :  N  =  3.38,  one  obtains 
9.1 1  X  3.38  =  30.79  grams  of  glucose  which  could  have  arisen 
from  the  protein  metabolism  of  the  time.  Since  47.42  grams 
were  actually  eliminated,  it  follows  that  the  difference  or 
16.63  grams  of  glucose  derived  their  origin  from  glycocoll. 

The  reaction  showing  this  conversion  of  glycocoll  into 
glucose  may  thus  be  written,  carbon  dioxid  being  neutralized 
by  ammonia  liberated  from  glycocoll  and  the  compound 
converted  into  urea. 


6C2H5N02   +   3CO2   +   3H2O    =    2C6H1206   +   3CH4NjO   +   3O2 
20  g.  glycocoll  =    16  g.  glucose   -f-    8  g.  urea 


190  SCIENCE   OF  NUTRITION 

It  should  be  noted  that  Cremer1  believes  that  only  three- 
quarters  of  the  carbon  passes  over  into  glucose  and  holds  the 
following  reaction  to  be  the  more  probable: 

4C2H6'N02  =    C6H1206   +    2CH4N2O 

20  g.  glycocoll    =    1 2  g.  glucose   +    8  g.  urea 

By  what  method  may  this  reaction  be  accomplished? 
It  has  been  shown  that  deamination  results  in  the  formation  of 
either  glyoxylic  acid,  CHO.COOH,  or  glycollic  acid,  CH2OH.- 
COOH.  These  materials  must  be  reduced  if  they  are  to 
form  glucose. 

Haas2  could  find  no  evidence  of  reduction  of  glyoxylic 
to  either  glycollic  or  acetic  acid  in  the  organism,  nor  was 
glycocoll  formed  synthetically  from  it  by  union  with  ammonia. 
Nor  could  Honjio3  find  any  indication  of  acetic  acid  formation 
after  perfusing  a  liver  with  glycollic  acid.  Also,  the  synthesis 
of  glycollic  acid  into  glycocoll  in  the  organism  cannot  be 
accomplished.4 

If  glycollic  acid  be  the  product  of  deamination,  as  appears 
most  probable,  its  first  reduction  product  would  be  glycol 
aldehyd. 

CH2OH.COOH     +     H2     =     CH2OH.CHO     +     H20 

Glycol  aldehyd  in  aqueous  solution  is  polymerized  with  the 
formation  of  sugar,5  C6H1206.  If  administered  by  subcuta- 
neous injection  to  a  rabbit  it  leads  to  an  output  of  sugar  in  the 
urine.6  When  perfused  through  the  liver  of  a  tortoise7  or  of  a 
dog8  glycol  aldehyd  is  converted  into  glycogen.  If  glycol 
aldehyd  be  slowly  administered  to  phlorhizinized  dogs,  as 
much  as  75  per  cent,  may  escape  oxidation  and  be  converted 
into  glucose.9 

1  Cremer:   " Medizinische  Klinik,"  1912,  viii,  2050. 

2  Haas:   " Biochemische  Zeitschrift,"  1912,  xlvi,  298. 

3  Honjio:   Ibid.,  1914,  lxi,  286. 

4  Sassa:   Ibid.,  1913-14,  lix,  353. 

6  Neuberg  and  Rewald:    "Biochemische  Handlexikon,"  ii,  266.^ 
•Mayer:   "Zeitschrift  fur  physiologische  Chemie,"  i903,_xxxviii,  151. 

7  Parnas  and  Baer:   "Biochemische  Zeitschrift,"  191 2,  xli,  392. 

8  Barrenscheen:   Ibid.,  1913,  lviii,  300. 

9  Sansumand  Woodyatt:  "Journal  of  Biological  Chemistry,"  i9i4,xvii,  521. 


THE   INFLUENCE    OF   PROTEIN   FOOD  191 

It  is  suggestive  in  this  connection  to  remember  that 
Neuberg1  has  shown  that  yeast  zymases  may  reduce  this 
simplest  of  all  the  oxy-aldehyds  into  ethylen  glycol: 

CHO  CH2OH 

CH2OH  CH,OH 

d-Alanin  (CH3.CHNH2.COOH.)— All  three  carbon  atoms 
arc  able  to  enter  into  the  formation  of  glucose.  Found  in  all 
true  proteins.  In  zein  as  much  as  ij.4  per  cent.,  in  muscle 
protein  about  8  per  cent,  is  present. 

Neuberg2  found  glycogen  in  the  liver  and  lactic  acid  in  the 
urine  of  a  normal  rabbit  following  the  ingestion  of  alanin. 
The  amino-acid  had  been  converted  into  lactic  acid  with  the 
elimination  of  ammonia.  Ringer  and  Lusk3  gave  20  grams  of 
i-alanin  to  a  phlorhizinized  dog  and  witnessed  its  complete 
elimination  in  the  form  of  urinary  glucose.  Dakin4  obtained 
the  same  result  after  administering  1-alanin. 

Mandel  and  Lusk5  showed  that  d-lactic  acid  was  completely 
converted  into  glucose  in  the  diabetic  organism  and  as  much  as 
70  per  cent,  of  the  d-1-lactic  acid  could  be  transformed. 

Dakin  has  emphasized  the  fact  that  these  experiments 
demonstrate  that  the  loss  of  asymmetry  of  the  central  carbon 
atom  of  1-alanin  or  of  1-lactic  acid  is  essential  for  the  formation 
of  d-glucose.  Such  a  loss  of  asymmetry  would  occur  in  the 
case  of  alanin  if  it  were  converted  into  pyruvic  acid  by  oxida- 
tive deamination. 


CH3 

CH3 

CHNH2 

+ 

0 

— > 

CO 

COOH 

Alanin. 

COOH 

Pyruvic  acid. 

1  Neuberg:   " Biochemische  Zeitschrift,"  1915,  lxxi,  1. 

2  Neuberg   and   Langstein:    "Archiv   fur  Physiologie,"  1903,  Suppl.  Bd., 

514- 

3  Ringer  and  Lusk:  Loc.  cit.  . 

i  Dakin  and  Dudley:    "Journal  of  Biological  Chemistry,"  1914,  xvii,  451. 
6  Mandel  and  Lusk:    "American  Journal  of  Physiology,"  1906,  xvi,  129. 


192  SCIENCE   OF   NUTRITION 

This  is  a  possible  pathway,  for  pyruvic  acid  is  convertible 
into  glucose  when  administered  to  the  glycosuric  organism.1 
Levene2  finds  that  aseptic  preparations  of  leukocytes  or 
kidney  tissue  effect  no  chemical  change  of  pyruvic  acid,  this 
being  contrary  to  the  action  of  yeast  cells  which  converts  it 
into  acetaldehyd  with  cleavage  of  C02  (see  p.  267). 

If  alanin  be  convertible  into  lactic  acid  by  hydrolysis,  the 
asymmetry  of  the  central  carbon  atom  could  be  eliminated  by 
a  reversed  internal  Cannizzaro  reaction,  as  follows: 
CH3  CH3  CH3 


CHNH2 

+ 

HOH 

► 

CHOH 

1               _ 

0 

-  II 

H2 

► 

CO    +    H20 

COOH 

Alanin. 

COOH 

Lactic  acid. 

CHO 

Methyl-glyoxal. 

The  Cannizzaro  reaction  involves  the  conversion  of  two 

molecules  of  aldehyd   into  one  of  acid   and   one  of  alcohol 

through  the  mediation  of  water.     Thus,  Batelli  and  Stern3 

observed  that  tissue  converted  acetaldehyd  into  alcohol  and 

acetic  acid. 

CH3  CH3 

I  I 

CHO  H2  CH2OH 

+  ► 

CH3  CH3 

I  I 

CHO  O  COOH 

The  enzyme  accomplishing  this  reaction  is  called  "  aldehyd 
mutase"  by  Parnas.4 

The  internal  Cannizzaro  reaction  deals  with  the  oxidation 
of  aldehyd  and  reduction  of  the  keto  radicles  in  the  same 
compound.  This  may  be  illustrated  by  the  conversion  of 
methyl  glyoxal  into  lactic  acid,  which  Dakin5  and  Neuberg6 
have  shown  is  rapidly  effected  by  tissue  in  vitro.     Dakin  calls 

1  Ringer:  "Journal  of  Biological  Chemistry,"  1913,  xv,  145;  1914,  xvii,  281; 
Dakin  and  Janney:  Ibid.,  1913,  xv,  177;  Cremer:  "Berliner  klinische  Wochen- 
schrift,"  1913,  1,  1457- 

2  Levene  and  Meyer:    "Journal  of  Biological  Chemistry,"  1914,  xvii,  443. 

3  Batelli  and  Stern:    "Compt.  rend.  soc.  biol.,"  1910,  lxviii,  742. 

4  Parnas:   " Biochemische  Zeitschrift,"  1910,  xxviii,  274. 

5  Dakin  and  Dudley:  "Journal  of  Biological  Chemistry,"  i9i3,xiv,  155,423. 

6  Neuberg:    "Biochemische  Zeitschrift,"  1913,  xlix,  502. 


THE  INFLUENCE  OF  PROTEIN  FOOD 


193 


the    enzymes   accomplishing   these    reactions   "glyoxylases," 
while  Neuberg  prefers  the  name  "keto-aldehyd  mutase." 


CH3 

I 
CO  H2 

I  + 

CHO  O 

Methyl  glyoxal. 


CH3 

CHOH 

I 
COOH 

Lactic  acid. 


The  reversed  internal  Cannizzaro  reaction  accomplishes 
the  conversion  of  lactic  acid  into  methyl-glyoxal. 

Dakin1  gave  9  grams  of  methyl  glyoxal  to  a  phlorhizinized 
dog  and  obtained  7  grams  of  extra  sugar  in  the  urine,  while 
12  grams  of  1-lactic  acid  yielded  9  grams  of  extra  glucose. 

These  experiments  enabled  Dakin  to  picture  the  trans- 
formation of  a  d-1-alanin  through  d-1-lactic  acid  into  d-glucose, 
as  follows: 


CH3 

CH3 

1 

CH2OH 

CH2OH 

HOCH      ► 

CO       — 

->    HCOH 

HCOH 

COOH 

CHO 

CHO 

HCOH 

CH3 

1 

CH3 

1 

CH2OH 

HOCH 

1 

HCOH       1 

•    CO       — 

->    HCOH 

HCOH 

COOH 

md  /-Lactic  acids.     R 

CHO 

lethyl-glyoxal. 

CHO 

o'-Glyceric  aldehyd. 

CHO 

d  -Glucose. 

Neuberg2  reached  essentially  similar  conclusions. 

Ringer  and  Lusk3  showed  that  glyceric  acid  was  convertible 
into  glucose  in  the  phlorhizinized  dog,  and  the  same  was  shown 
for  glyceric  aldehyd  by  Woodyatt.4 

It  has  been  difficult  to  find  a  chemical  analogy  to  the 
transformation  of  the  CH3  group  of  methyl-glyoxal  into 
-CHoOH  in  glycerin  aldehyd.  It  is  certain  that  the  CH3 
groups  in  lactic  acid  and  alcohol  both  arise  in  biochemical 
reactions  from  glucose,  yet  the  manner  of  origin  is  unknown.5 

1  Dakin  and  Dudley:   "Journal  of  Biological  Chemistry,"  1913,  xv,  127. 

2  Neuberg:  "Biochemische  Zeitschrift,"  1913,  li,  484- 

3  Ringer  and  Lusk:   "Loc.  cit. 

4  Woodyatt:  "Journal  of  Biological  Chemistry,"  1915,  xxi,  1. 

6  Neuberg  and  Rewald:    "Biochemische  Zeitschrift,"  1914*  lxvii,  127. 

13 


194  SCIENCE   OF   NUTRITION 

Dakin  (oral  statement  to  the  writer)  presents  a  solution  of 
the  problem  dependent  upon  the  interconversion  of  tauto- 
meric forms  of  methyl-glyoxal : 

CH3  CH2  OH  CH2OH 

I      >     II      +  I 

CO         COH     H        CHOH 

L   * —   .1  I 

CHO        CHO   ►        CHO 

Methyl-  Methyl-  Glyceric 

glyoxal.  glyoxal.  aldehyd. 

Since  fructose1  and  many  other  hexose  sugars  yield  methyl- 
glyoxal  with  readiness  in  vitro,  there  is  much  likelihood  that 
this  is  the  intermediary  substance  produced  when  fructose 
and  galactose,  for  example,  are  converted  into  glucose  by  the 
diabetic  or  into  glycogen  (which  yields  glucose)  in  the  normal 
organism.  The  above  described  transformation,  first  postu- 
lated by  Nef,2  is,  therefore,  of  fundamental  biologic  signifi- 
cance not  only  in  the  metabolism  of  alanin  but  also  as  regards 
that  of  carbohydrate. 

It  may  be  added  that  alanin  may  be  formed  synthetically 
from  pyruvic  acid,3  when  this  substance  is  perfused  through 
the  liver,  or  from  glycogen4  when  an  ammonium  salt  is  per- 
fused through  a  liver  rich  in  glycogen. 

It  appears  from  this  analysis  that  the  amino-acid  alanin 
yields  on  deamination  an  acid  which  may  readily  be  converted 
into  glucose  or  into  methyl-glyoxal,  a  direct  cleavage  product 
of  glucose,  and  which,  therefore,  may  behave  like  glucose  in 
the  organism.  Consideration  of  the  oxidation  of  glucose  will 
be  found  in  Chapter  IX. 

Valin  ((CH3)2:  CH.CHNH2.COOH).— Present  in  small 
amounts  in  most  proteins.     Fate  obscure. 

By  the  method  of  liver  perfusion,  Embden,  Salomon,  and 
Schmidt5  could  find  no  acetone  bodies  arising  from  valin. 

1Wohl:   "Biochemische  Zeitschrift,"  IQ07,  v,  45. 

2  Nef:    "Liebig's  Annalen,"  1904,  cccxxxv,  247. 

3  Embden  and  Schmitz:  "Biochemische  Zeitschrift,"'  1911-12,  xxxviii,  393. 

4  Fellner:   Ibid.,  1911-12,  xxxviii,  414. 

6  Embden,  Salomon,  and  Schmidt:  " Hofmeister's  Beitrage,"  1906,  viii, 
129. 


THE   INFLUENCE    OF   PROTEIN   FOOD  195 

Dakin1  gave  valin  to  a  phlorhizinized  dog,  but  could  find 
no  clear  evidence  of  glucose  or  /3-oxybutyric  acid  formation 
from  it.  Its  oxy-acid,  a-oxy-isovalerianic  acid,  also  yielded 
little  or  no  sugar. 

Leucin  ((CH3)2:  CH.CH2.CHNH2COOH).— Present  in  all 
proteins.    Convertible  into  (3-oxybutyric  acid. 

Leucin  when  given  to  a  phlorhizinized  dog  produces  little 
or  no  glucose.2  When  added  to  a  perfusing  fluid  and  passed 
through  a  surviving  liver  leucin  yields  acetone  bodies  in  large 
amounts.3  Baer  and  Blum4  found  a  greatly  increased  out- 
put of  /3-oxybutyric  acid  after  giving  33.7  grams  of  leucin  to  a 
diabetic  patient.  The  chemical  reaction  undoubtedly  follows 
the  known  laws  of  oxidation  on  the  a-amino  group  of  the  amino- 
acids  of  jS-oxidation  and  cleavage  of  a  methyl  radicle  whose 
further  fate  is  unknown.  These  reactions  may  thus  be  pre- 
sented : 


CH3  CH3 

\/ 

CH 

CH3     CH3 

\/ 
CH 

CH3    ICHj 

CH3 

/3CH 

CHOH 

CH2 

> 

CH2  -          > 

CH2            — 

->        CH2 

CHNH2 

COOH 

Leucin. 

HOH          CHOH        02 

1 
COOH 

Oxyisobutyl  acetic  acid. 

COOH 
COo  +  H20 

Isovaleric  acid. 

COOH 

/3-Oxybutyric  acid. 

The  end-product  of  the  metabolism  of  leucin  is,  therefore, 
the  same  as  the  end-product  of  ordinary  fat  metabolism. 

Phenylalanin,  C6H5.CH2.CHNH2COOH,  and  Tyrosin, 
HO.C6H4.CH2.CHNH2COOH .—  Yield  (3-oxybutyric  acid,  and 
in  alca  ptonuria  homogentisic  acid.  Present  in  all  proteins, 
except  that  tyrosin  is  absent  in  gelatin. 

The  metabolism  of  these  substances  has  already  been  con- 
sidered in  some  detail  (see  p.  178).  Embden  and  Baldes5 
state  that  when  phenylalanin  is  added  to  the  perfusing  fluid 

1  Dakin:    "journal  of  Biological  Chemistry,"  1913,  xiv,  321. 

2  Halsey:   "American  Journal  of  Physiology,"  1904,  x,  229;  Dakin:  Loc.  cit. 

3  Embden,  Salomon,  and  Schmidt:   Loc.  cit. 

4  Baer  and  Blum:    "Arch.  f.  ex.  Path,  und  Pharm.,"  1906,  lv,  89. 

5  Embden  and  Baldes:    " Biochemische  Zeitschrift,"  1913,  lv,  301. 


196  SCIENCE   OF   NUTRITION 

passing  through  the  liver  it  may  be  converted  into  tyrosin. 
Even  though  phenylalanin  does  not  always  yield  tyrosin  in  the 
organism,  yet  it  is  believed  that  it  may  be  converted  into 
p-oxyphenylpyruvic  acid,  which  is  the  first  oxidation  product 
of  tyrosin. 

In  the  phenomenon  called  alcaptonuria  (see  p.  178),  tyrosin 
and  phenylalanin  are  believed  to  be  oxidized  only  as  far  as 
homogentisic  acid,  in  which  form  they  appear  in  the  urine. 
Falta1  reports  that  if  phenylalanin  or  tyrosin  be  administered 
in  alcaptonuria  each  is  completely  converted  into  homogentisic 
acid  and  so  eliminated.  In  alcaptonuria  the  ratio  between 
homogentisic  acid  and  nitrogen  elimination  in  the  urine  is 
quite  constant,  being  45  :  100  or  50 :  ioo,2  and  the  distribution 
of  the  various  other  nitrogenous  compounds  in  the  urine  re- 
mains normal. 

Neubauer  and  Falta3  emphasized  the  idea  that  homogen- 
tisic acid  is  always  formed  in  normal  metabolism,  but  in  this 
rare  disease  cannot  be  oxidized.  The  power  to  split  the 
benzol  ring  was  absent. 

However,  Dakin4  has  administered  to  alcaptonurics  para- 
methylphenylalanin,  CH3.C6H4.CH2CHNH2COOH,  and  para- 
methoxyphenylalanin,  CH3O.C6H4.CH2CHNH2COOH,  sub- 
stances which  cannot  undergo  the  quinoid  transformation, 
(see  p.  178)  and  has  found  that  these  are  oxidized  in  the 
organism.  He,  therefore,  concludes  that  the  formation  of 
homogentisic  acid  in  metabolism  is  always  pathologic,  and 
that  the  benzol  ring  can  be  broken  even  in  alcaptonuria  with- 
out its  intermediation.  Fromherz  and  Hermanns5  believe 
that  the  aromatic  amino-acids  normally  follow  a  dual  path  to 

1  Falta:   " Biochemisches  Centralblatt,"  1904-05,  iii,  175. 

2Langstein  and  Meyer:  "Deutsches  Archiv  fur  klinische  Medizin,"  1903, 
lxxviii,  161;  Schumm:  "Munchener  med.  Wochenschrift,"  1904,  li,  1599; 
Garrod  and  Hele:  "Journal  of  Physiology,"  1905,  xxxiji,  205;  Ravold  and 
Warren:    "Journal  of  Biological  Chemistry,"  1909-10,  vii,  465. 

3  Neubauer  and  Falta:  "Zeitschrift  fur  physiologische  Chemie,"  1904, 
xlii,  81. 

4  Dakin:   "Journal  of  Biological  Chemistry,"  1911,  ix,  151. 

5  Fromherz  and  Hermanns:  "Zeitschrift  fur  physiologische  Chemie,"  1914, 
xci,  194. 


THE  INFLUENCE  OF  PROTEIN  FOOD 


197 


destruction  and  that  one  of  these  is  closed  in  alcaptonuria, 
whereas  the  other  remains  open.  They  present  this  picture 
of  the  process : 


3  :  4  Dioxyphenyl- 
acetic  acid 


Muconic  acid 
->  closed  in  alcaptonuria. 


Quinon 
acetic  acid 


It  will  be  recalled  that  muconic  acid  has  been  considered  as 
representing  the  opening  door  of  the  benzol  ring,  ever  since 
Taffe1  gave  benzol  to  a  rabbit  and  found  muconic  acid  in  the 
urine. 

Phenylalanin,  ty rosin,  homogentisic  acid,2  and  muconic 
acid3  all  yield  acetone  bodies  when  perfused  through  a  surviv- 
ing liver. 

The  reaction  involving  the  production  of  /3-oxy butyric  acid 
cannot  yet  be  written,  though  two  of  its  four  carbon  atoms 
are  probably  derived  from  the  phenyl  ring  and  two  from  the 
side  chain.4 

Tyrosin  yields  no  sugar  in  the  phlorhizinized  dog,5  nor  does 
phenylalanin.6 

When  the  ammonium  salts  of  the  keto-acids  corresponding 
to  phenylalanin  and  tyrosin  are  perfused  through  a  surviving 

1  Jaffe:    "Zeitschrift  fur  physiologische  Chemie,"  1909,  Lxii,  58. 

2  Embden,  Salomon,  and  Schmidt:   Loc.  cit. 

3Hensel  and  Riesser:  "Zeitschrift  fur  physiologische  Chemie,"  1913, 
lxxxviii,  38. 

4Wakeman  and  Dakin:  "Journal  of  Biological  Chemistry,"  1911,  ix,  139. 

6  Ringer  and  Lusk:  Loc.  cit.;  confirmed  by  Dakin. 

6  Dakin:   "Journal  of  Biological  Chemistry,"  1913,  xiv,  321. 


198  SCIENCE   OF    NUTRITION 

liver  there  may  be  a  synthetic  production  of  the  two  last- 
named  substances.1  The  reaction  of  deamination  is,  therefore, 
reversible  in  these  cases. 

1-Serin,  CH2OH.CHNH2COOH. — Detected  in  small  quan- 
tities in  many  proteins.  Three  carbon  atoms  are  able  to  enter 
into  the  formation  of  glucose. 

Dakin2  showed  that  the  ingestion  of  11.9  grams  of  serin 
by  a  phlorhizinized  dog  resulted  in  the  excretion  of  1 1  grams  of 
extra  glucose  in  the  urine.  One  might  picture  the  conversion 
of  serin  into  glyceric  acid  which  Ringer  and  Lusk  (p.  193) 
showed  is  transformed  into  glucose: 

CH2OH  CH2OH 

CHNH2     +     HOH  CHOH 

I  I 

COOH  COOH 

1-Serin.  Glyceric  acid. 

But  in  order  to  remove  the  asymmetry  of  the  central  carbon 
atom  it  seems  more  probable  that  a  keto-body  is  an  inter- 
mediary oxidative  product.  The  transformation  might  take 
the  following  form: 

CH2OH  CH2OH  CH2OH 

CHNH2        ►        CO  ►         CHOH 

COOH  CHO  CHO 

1-Serin.  a-keto-(3-oxypropionic  aldehyd.     d-glyceric  aldehyd. 

Cystin,  S— CH2.CHNH2COOH  —  Present    in    most     proteins. 

S— CH2.CHNH2COOH 
Six  carbon  atoms  probably  may  enter  into  the  formation  of  glucose. 
In  a  rare  disease  called  cystinuria  cystin  appears  dissolved 
in  the  urine,  or  it  may  take  the  form  of  stone  or  of  sediment. 
If  cystin  be  administered  to  a  normal  person  it  is  oxidized,  and 
does  not  alter  the  normal  relation  between  oxidized  and 
unoxidized  sulphur  in  the  urine.3  If  cystin  be  given  to  a 
patient  with  cystinuria  a  part  is  eliminated,  but  a  still  greater 

1  Embden  and  Schmitz:   " Biochemische  Zeitschrift,"  1910,  xxix,  423, 

2  Dakin:   Loc.  cit. 

3  Blum:   "Hofmeister's  Beitrage,"  1904,  v,  1. 


THE  INFLUENCE  OF  PROTEIN  FOOD  1 99 

part  is  oxidized.1  The  disturbance,  therefore,  is  not  complete. 
When  protein  is  given  in  increased  measure  the  cystin  elimina- 
tion is  increased  in  the  cystinuric  patient.2  The  increase  in 
neutral  sulphur  found  in  the  urine  is  at  the  expense  of  the 
alkaline  sulphate  usually  found  there. 

In  normal  metabolism  cystin  is  probably  first  broken  up 
into  two  molecules  of  cystein,  for  on  giving  brombenzol 
mercapturic  acid  appears  in  the  urine.  This  acid  is  a  compound 
of  cystein,  brombenzol,  and  acetic  acid.  The  reaction,  as 
shown  by  Friedmann,3  takes  place  as  follows: 

CH,SH  CH2S.C5H4.Br 

CHNH2     +     C6H5Br     +     CH3COOH     =     CHNH.CO.CH3     +     H2 

COOH  COOH 

Cystein.  Brombenzol.  Acetic  acid.        Brombenzol  mercapturic 

acid. 

This  affords  an  example  of  acetylation  not  uncommon  in 
the  organism.4  Acetic  acid  is  probably  constantly  available, 
being  derived  from  the  metabolism  of  fat  (see  p.  302). 

Marriott  and  Wolf5  further  investigated  this  condition  of 
artificially  induced  cystinuria,  and  were  able  to  increase  the 
unoxidized  sulphur  (cystein-S)  in  the  urine  fourfold  by  this 
means,  and  nearly  to  remove  all  the  oxidized  sulphur.  The  sul- 
phur was,  therefore,  not  oxidized  to  sulphate  as  in  the  normal 
state.  That  cystein  is  the  mother  substance  of  the  taurin  of 
the  bile  Friedmann6  illustrates  in  accordance  with  the  following 
formula : 


CH2SH 

CH2S03H 

CH2S03H 

CHNHo 

+      30          - 

-*        CHNH2           — 

-»        CHNH2 

COOH 

Cystein. 

COOH 

Cysteinic  acid. 

C02 

Taurin. 

1  Williams  and  Wolf:    "Journal  of  Biological  Chemistry,"  1909,  vi,  337. 

2  Alsberg  and  Folin:   "American  Journal  of  Physiology,"  1905,  xiv,  54. 

3  Friedmann:    " Hofmeister's  Beitrage,"  1904,  iv,  486. 

4  Consult  von  Fiirth:    "Probleme  der  physiologischen  und  pathologischen 
Chemie,"  Leipzig,  1913,  ii,  p.  465. 

5  Marriott  and  Wolf:  "American  Medicine,"  1905,  be,  1026.    See  also  Zeller 
and  Straczewski:    "Archiv  fur  Physiologie,"  1914,  p.  585. 

6  Friedmann:   "Hofmeister's  Beitrage,"  1903,  iii,  1. 


200  SCIENCE   OF   NUTRITION 

Taurin,  however,  is  not  the  only  pathway  of  cystein  de- 
struction, for  Dakin1  gave  a  phlorhizinized  dog  15.7  grams  of 
cystein,  which  theoretically  is  convertible  into  at  most  11.6 
grams  of  glucose,  and  found  12.2  grams  of  extra  glucose  in  the 
urine.  This  transformation  would  be  conceivable  through 
hydrolysis  and  the  conversion  of  cystein  into  serin,  which,  as 
already  stated,  is  convertible  into  glucose. 


CHoSH 

CH2OH 

CHNH2 

+    HOH 

> 

CHNH2     +     H2S 

COOH 

Cystein. 

COOH 

Serin. 

Dakin  made  note  of  the  fact  that  the  sulphur  excretion 
under  the  conditions  of  his  experiments  was  in  the  form  of 
sulphate  and  was  relatively  very  slow.  This  is  contrary  to 
the  usual  behavior  of  the  sulphur  contained  in  cystein  (see 
p.  168). 

It  is  evident  that  cystein  metabolism  has  the  choice  of  at 
least  two  different  pathways  in  the  organism. 

Aspartic  Acid,  HOOC.CH2.CHNH2.COOH—  Present  in 
most  proteins.  Three  carbon  atoms  enter  into  the  formation  of 
glucose. 

Aspartic  acid  was  given  to  phlorhizinized  dogs  by  Ringer 
and  Lusk2  and  the  equivalent  of  three  carbon  atoms  was 
recovered  as  glucose  in  the  urine.  This  has  been  confirmed 
in  Cremer's  laboratory  by  Hering,3  who  administered  aspar- 
agin.  The  possible  pathways  of  this  transformation  are  sev- 
eral.    Ringer  and  Lusk  gave  the  following  course: 


COOH 

COOH 

COOH 

CH2 

1 

CH2 

CH2 

CHNH2 

CHOH 

1 

CH,OH 

COOH 

Aspartic  acid. 

COOH 

Malic  acid. 

C02 

/3-Lactic  acid. 

1  Dakin:   Loc.  cit. 

2  Ringer  and  Lusk:   Loc.  cit. 

8  Hering:   "Cremer's  Beitrage  zur  Physiologie,"  1914,  i,  1. 


THE    INFLUENCE    OF    PROTEIN    FOOD  201 

Later  Ringer1  found  that  malic  acid  was  in  large  measure 
convertible  into  glucose. 

This  conception  of  intermediary  reaction  is  supported  by 
the  finding  of  Ackermann2  that  digestion  of  aspartic  acid  with 
putrid  pancreas  produces  /3-alanin,  H2NCH2.CH2.COOH. 

Dakin3  considers  that  alanin  or  lactic  acid  are  the  primary 
cleavage  products  of  aspartic  acid  metabolism,  and  this  is 
attested  by  the  researches  of  Meyer4  in  Neuberg's  laboratory, 
who  finds  that  tissue  pulp  of  liver  and  muscle  convert  keto- 
succinic  acid  into  pyruvic  acid.  The  reaction  would  then 
take  place  as  follows: 


glucose 


One,  or  perhaps  both,  of  these  pathways  are  open  in  the 
organism  for  the  metabolism  of  aspartic  acid  and  for  synthesis 
of  glucose  from  it  should  conditions  favor. 

Glutamic  Acid,  HOOC.CH2.CH2.CHNH2.COOH.— Present 
in  all  proteins,  frequently  largest  constituent  amino-acid  in  the 
molecule,  as  in  gliadin  of  wheat  (44  per  cent.)  and  in  muscle 
{22  per  cent.).  Three  carbon  atoms  enter  into  the  formation  of 
glucose. 

This  was  the  first  amino-acid  whose  power  to  form  glucose 
was  measured.5  Ringer  and  Lusk  held  that  this  power  to 
form  glucose  was  through  /3-oxidation  of  the  central  carbon 
atom,  as  follows: 

1  Ringer,  Frankel,  and  Jonas:  "Journal  of  Biological  Chemistry,"  1913,  xiv, 

539- 

2  Ackermann:   "Zeitschrift  fur  Biologie,"  1911,  Ivi,  87. 

3  Dakin:   hoc.  cit. 

4  Mayer,  P.:   " Biochemische  Zeitschrift,"  1914,  lxii,  462. 

6  Lusk:    "American  Journal  of  Physiology,"  1908,  xxii,  174. 


COOH 

COOH 

C02 

CH2 

>        CH2 

»         CH3 

CHNH2 

CO 

CO    » 

COOH 

Aspartic  acid. 

COOH 

Keto-succinic 

acid. 

COOH 

Pyruvic  acid. 

202 


SCIENCE   OF   NUTRITION 


COOH 

COOH 

CH2 

> 

CH3 

CH2 

+ 

HOH 

CH2OH 

CHNH2 

+ 

HOH 

CHOH 

COOH 

Glutamic  acid. 

COOH 

Glyceric  acid 

Since  glyceric  acid  forms  glucose,  this  pathway  would  be 
a  natural  one.  Dakin  agrees  with  this  as  possible.  Warkalla1 
confirms  the  synthesis  of  three  carbon  groups  of  glutamic  acid 
into  glucose. 

F.  Ehrlich2  showed  that  fermenting  yeast  converted 
glutamic  acid  into  succinic  acid,  HOOC.CH2.CH2.COOH,  and 
Neuberg3  finds  that  keto-glutaric  acid,  HOOC.CH2.CH2.CO.- 
COOH,  yields  the  same  product  under  similar  conditions. 
This  indicates  keto-glutaric  acid  as  a  probable  intermediary 
product.  Since  Ringer4  has  shown  that  succinic  acid  is 
convertible  into  glucose,  this  appears  to  be  a  possible  pathway 
of  the  decomposition  of  glutamic  acid. 

According  to  Abderhalden,5  glutamic  acid  may  be  con- 
densed into  pyrrolidon  carboxylic  acid.  The  conversion 
of  this  into  prolin  or  pyrrolidin  carboxylic  acid  has  not 
yet  been  achieved. 


COOH 

1 
CH2 

CO 

1  \ 

CH2 

I 

CH2 

l\ 
CH2 

1 

CH2 

CH2 

CH2 

CHNH2 

CHNH 

CHNH 

COOH 

Glutamic  acid. 

COO 

Pyrrolidon  c 
acic 

H 

arboxylic 

COO 

Pyrrolidin 
acic 

H 

:arboxylic 

1  Warkalla:    "Cremer's  Beitrage,"  1914,  i,  91. 

2  Ehrlich,  F.:   "Biochemische  Zeitschrift,"  1909,  xviii,  391. 

3  Neuberg  and  Ringer,  M.:    Ibid.,  1915,  lxxi,  226. 

4  Ringer,  Frankel,  and  Jonas:     "Journal  of  Biological  Chemistry,"  1913, 
xiv,  539. 

5  Abderhalden  and  Kautzsch:     "Zeitschrift  fur  physiologische  Chemie," 
1910,  lxviii,  487. 


THE  INFLUENCE  OF  PROTEIN  FOOD  203 

Pyrrolidin  carboxylic  acid  made  in  some  such  manner  may 
become  the  mother  substance  used  in  the  construction  of 
hemoglobin  in  the  animal  or  of  chlorophyll  in  the  plant. 

Lysin,  NH2.CH2.CH2.CH2.CH2.CHNH2.COOH.— Present 
in  proteins  of  animal  origin.  Absent  in  zein  and  present  in 
very  small  amount  in  such  a  vegetable  protein  as  gliadin.  It  is 
the  only  amino-acid  with  a  straight  chain  which  does  not  form 
glucose. 

Dakin1  gave  lysin  to  a  phlorhizinized  dog,  but  found  neither 
extra  sugar  nor  an  increase  in  the  /3-oxybutyric  acid  excretion 
in  the  urine.  This  is  explained  by  Ringer2  on  the  ground  that 
lysin  maybe  converted  into  glutaric  acid,  HOOC.C3H6.COOH, 
which  does  not  form  glucose  when  administered  in  phlorhizin 
glycosuria.3  The  small  increase  in  /3-oxybutyric  acid  elimina- 
tion noted  by  Ringer  in  this  experiment  does  not  necessarily 
indicate  that  this  substance  is  an  intermediary  metabolism 
product. 

The  oxidation  to  COOH  of  the  e-C,  to  which  an  NH2 
group  is  attached,  followed  by  /3-oxidation,  would  yield 
aspartic  acid,  provided  the  NH2  in  the  e-position  remained 
untouched.  Such  a  course  of  metabolism  would  cause  lysin 
to  yield  glucose  in  abundance  and  is  therefore  excluded. 

Bacteria  in  intestinal  putrefaction  convert  lysin  into 
cadaverin,  NH2 — C5Hi0 — NH2,  through  simple  C02  cleavage. 
In  severe  cases  of  cystinuria  the  diamines  cadaverin  and 
putresin  (see  p.  204)  appear  in  the  urine  and  this  constitutes 
diaminuria.4 

Arginin,  NH2.CNHNH.CH2CH2CH2.CHNH2.COOH.— 
Present  in  most  proteins.  Probably  three  carbon  atoms  form 
glucose. 

Kossel  and  Dakin5  found  that  liver  but  not  muscle  con- 

1  Dakin:    hoc.  cit. 

2  Ringer,  Frankel,  and  Jonas:    Loc.  cit. 

3  Ringer:    "Journal  of  Biological  Chemistry,"  191 2,  xii,  223. 

4  Literature,  v.  Fiirth:  "Probleme  der  physiologischen  und  pathologischen 
Chemie,"  1913,  Bd.  II,  p.  117. 

5  Kossel  and  Dakin:  "Zeitschrift  fur  physiologische  Chemie,"  1904,  xli, 
321;  1904,  xlii,  183. 


204  SCIENCE    OF   NUTRITION 

tained  an  enzyme  capable  of  splitting  d-arginin  into  urea  and 
ornithin,  the  only  reaction  by  which  urea  is  obtained  as  a 
simple  cleavage  product  of  an  amino-acid.  Dakin1  gave  both 
arginin  and  ornithin  to  a  phlorhizinized  dog,  and  witnessed  a 
sufficient  elimination  of  extra  glucose  to  account  for  three  of 
the  carbon  atoms  in  these  substances.  Since  three  carbon 
atoms  of  succinic  acid  enter  into  the  formation  of  glucose,  and 
succinic  acid  appears  to  be  a  possible  product  of  the  metab- 
olism of  ornithin,  one  may  assume  that  this  might  represent  the 
pathway  into  sugar.     These  formulae  may  thus  be  portrayed: 


glucose 


HN:C.NHCH2 

NH2    | 

CH2 

CH2NH2 
CH2 

COOH 

1 
CH2 

CH2          - 

-»     CH2          ► 

CH2 

CHNH2 

CHNH2 

| 

COOH 

Succinic  acid. 

COOH 

Arginin. 

COOH 

Ornithin. 

Another  possible  pathway  would  be  the  oxidation  of  the 
o-C  atom  of  ornithin  to  COOH,  with  the  production  of  glutamic 
acid,  which  would  then  break  up  with  sugar  formation  (see  p. 

20l). 

Bacteria  in  the  intestine  may  convert  ornithin  into 
putresin,  NH2— C4H8 — NH2,  through  the  cleavage  of  C02 
(see  p.  203). 

Arginin  is  the  only  amino-acid  containing  the  guanidin 
nucleus,  which  is  also  found  in  creatin.  However,  attempts 
to  associate  the  origin  of  creatin  from  arginin  have  proved 
fruitless.  Jaffe2  gave  nitrate  of  arginin  subcutaneously  to  a 
rabbit,  but  found  no  change  in  the  amount  of  creatin  in  the 
urine  or  muscle.  According  to  the  known  laws  of  oxidation  of 
amino-acids,  guanidin  acetic  acid,  NH2.CNH.NH.CH2.COOH, 
might  readily  be  an  oxidation  product  of  arginin.  When 
Jaffe  gave  this  substance  to  a  rabbit  he  found  that  a  methyl 

1  Dakin:   Loc.  cit. 

2  Jaffe:   "Zeitschrift  ftir  physiologische  Chemie,"  1906,  xlviii,  430. 


THE  INFLUENCE  OF  PROTEIN  FOOD  205 

group  was  added  and  it  was  in  part  eliminated  in  the  urine 
as  creatin,  NH2.CNH.NCH3.CH2.COOH.  The  proof  of  the 
origin  of  guanidin  acetic  acid  in  the  organism  is,  however, 
lacking.  Arginase  does  not  effect  the  cleavage  of  creatin  or 
guanidin  acetic  acid1  (see  also  p.  209).  \ 

Histidin,  N  :  CH.NH.CH  :  C.CH2.CHNH2.COOH.— 
Present  in  most  proteins.  Does  not  produce  glucose,  and  there 
is  no  clear  evidence  that  it  produces  (3-oxybutyric  acid. 

When  histidin  is  given  to  dogs  it  is  oxidized  and  urea  formed 
from  it  appears  in  the  urine.2  When  it  is  given  to  phlor- 
hizinized  dogs  Dakin3  finds  no  clear-cut  evidence  that  it  is 
converted  either  into  glucose  or  /3-oxybutyric  acid. 

Histidin  gives  Ehrlich's  diazo-reaction,  and  is  probably  the 
chromogen  within  urochrom.4 

Prolin,  NH.CH2.CH2.CH2.CH.COOH.— Present  in  most 
proteins.     Three  carbon  atoms  enter  into  the  formation  of  glucose. 

Dakin5  gave  prolin  to  a  phlorhizinized  dog  and  found 
extra  glucose  eliminated  to  the  extent  of  three  of  the  five 
carbon  atoms  contained  in  prolin.  Ringer  suggests  that  the 
intermediary  product  may  be  succinic  acid,  but  lactic  acid  or 
glyceric  acid  are  also  possible.  The  metabolism  probably  fol- 
lows the  same  lines  as  does  that  of  glutamic  acid  (see  p.  202). 

Tryptophan  {Formula  below). — Present  in  animal  proteins 
except  gelatin.  Absent  in  zein.  Produces  neither  glucose  nor 
fi-oxybutyric  acid,  but  is  convertible  into  kynurenic  acid. 

Dakin6  could  find  no  certain  increase  in  sugar  or  /3-oxy- 
butyric acid  excretion  after  giving  14.5  grams  of  tryptophan 
to  a  phlorhizinized  dog. 

Ellinger7   discovered    that   the   production   of   kynurenic 

1  Dakin:    "Journal  of  Biological  Chemistry,"  1907,  iii,  435. 

2  Abderhalden  and  Einbeck:  "Zeitschrift  fur  physiologische  Chemie,"  1909, 
lxii,  322;  1910,  lxviii,  395. 

3  Dakin:    "Journal  of  Biological  Chemistry,"  1913,  xiv,  328. 

4  von  Furth:  "Probleme  der  physiologischen  und  pathologischen  Chemie," 
1913,  ii,  605. 

5  Dakin:    "Journal  of  Biological  Chemistry,"  1912-13,  xni,  513. 

6  Dakin:    Ibid.,  1913,  xiv,  321. 

7  Ellinger:    "Zeitschrift  fur  physiologische  Chemie,"  1904,  xliii,  325. 


206 


SCIENCE    OF   NUTRITION 


acid,  which  had  long  been  known  as  a  component  of  dog's 
urine,  was  largely  increased  after  giving  tryptophan.  Mendel 
and  Jackson1  found  that  the  kynurenic  acid  elimination  in 
dogs  varied  directly  with  the  protein  metabolism,  but  was  not 
derived  from  gelatin  metabolism.  Ellinger  also  gave  trypto- 
phan to  a  rabbit,  whose  urine  normally  contains  no  kynu- 
renic acid,  and  found  kynurenic  acid  in  the  urine.  Rabbits 
however,  normally  oxidize  kynurenic  acid  when  ingested  in 
small  amounts.  He  reaches  the  conclusion  that  animals  in 
general  may  produce  kynurenic  acid,  and  that  this  is  usually 
readily  oxidized  except  in  the  organism  of  the  dog,  where  it  is 
only  partly  destroyed,  and  therefore  appears  in  the  urine. 

Hopkins  and  Cole2  first  isolated  tryptophan  in  a  state  of 
purity  and  determined  its  formula.  Miss  Homer3  determined 
the  exact  formula  of  kynurenic  acid.  Ellinger4  thus  presents 
the  transformation  of  tryptophan  into  kynurenic  acid: 


H2N.CH.COOH 

\ 
/CH2 

-c/ 


N 


CH 

\ 

NH 

Tryptophan. 
Indol  aminopropionic  acid. 


=  C.COOH 
\  , 
CH 

/ 

-C 

OH 


Kynurenic  acid. 
7-oxy-a-quinolin  carboxylic  acid. 


/     V 


\ 


Intestinal  bacteria  act  upon  the  propionic  acid  radicle  of 
tryptophan  and  convert  it  into  skatol  or  indol: 


CeH^ 


C— CH3 

CH 

'       \ 

/       ' 

CH 

C6H4 

s          / 

\ 

NH 

NH 

Skatol. 

Indol 

% 


CH 


1  Mendel  and  Jackson:    "American  Journal  of  Physiology,"  1898-99,  ii,  1. 

2  Hopkins  and  Cole:    "Journal  of  Physiology,"  1901-02,  xxvii,  418. 

3  Homer:  "Journal  of  Biological  Chemistry,"  1914,  xvii,  509. 

4  Ellinger  and  Matsuoka:  "Zeitschrift  fiir  physiologische  Chemie,"  1914? 
xci,  45- 


THE    INFLUENCE    OF   PROTEIN   FOOD  207 

Indol  and  skatol,  together  with  phenol,  C6H5.OH,  and  p- 
cresol,  CH3.C6H4.OH,  the  products  of  bacterial  putrefaction 
of  phenylalanin  and  ty rosin,  are  conjugated  with  sulphuric 
acid  in  the  liver  and  are  eliminated  as  ethereal  sulphates  in  the 
urine. 

Summary. — It  has  been  noted  that  in  completely  phlo- 
rhizinized  dogs  the  actual  D  :  N  ratio  is  3.65  :  1.  How  ac- 
curately may  one  calculate  the  theoretic  origin  of  glucose 
from  the  present  amount  of  information  at  hand?  If  the 
analysis  of  muscle  tissue  given  by  Osborne  (see  p.  77)  be 
taken,  one  may  estimate  how  much  sugar  may  arise  from  the 
various  fragments  of  the  protein  molecule. 

CALCULATION  SHOWING  THE  ORIGIN  OF  GLUCOSE  FROM 

PROTEIN 

From  ioo  Grams  of  Protein. 
Substance.  Amino  Acid.         Glucose. 

Grams.  Grams. 

Glycocoll 4.0  3.2 

Alanin 8.1  8.2 

Aspartic  acid 10.6  7.2 

Glutamic  acid 22.3  13.6 

Prolin 8.0  6.3 

Arginin 11.5  5.9 

Cystin  * 

Serin* 

64.5  44-4 

*  Amount  not  given. 

Since  100  grams  of  the  ox  muscle  contained  16.18  grams 
of  nitrogen  and  from  this  same  material  44.4  grams  of  glucose 
may  be  calculated  to  arise,  one  may  deduce  the  equation, 
D  :  N  =  Y6j&  =  2.75  : 1.  If  the  D  :  N  ratio  is  3.65,  59  gm.  of 
glucose,  or  14.6  gm.  more  than  the  quantity  above  estimated, 
are  eliminated  in  the  urine  when  100  gm.  of  protein  are 
destroyed.  These  14.6  gm.  represent  an  additional  amount  of 
glucose,  whose  origin  is  unexplained  and  which  is  equal  to  24 
per  cent,  of  the  total  maximal  production.  Such  sources  of 
sugar  might  be  cystin,  which,  if  all  the  sulphur  in  protein  were 
in  that  form,  might  at  most  yield  2  grams  of  glucose,  serin 
whose  solubility  prevents  accuracy  of  determination,  and 
glycocoll  formed  synthetically. 


208  SCIENCE    OF   NUTRITION 

Though  the  analytic  methods  are  admittedly  crude,  yet 
they  give  some  insight  into  the  possibilities  of  transformation 
of  a  heterogeneous  medley  of  amino-acids  into  a  common 
substance,  glucose,  the  carbohydrate  of  the  organism.1 

Leucin,  tyrosin,  and  phenylalanin,  on  the  other  hand, 
yield  /3-oxybutyric  acid,  or  the  end-product  characteristic  of 
fat  metabolism,  whereas  the  final  products  of  valin,  lysin, 
histidin,  and  tryptophan  are  unknown. 

ADDENDUM  CONCERNING  THE  COMPOSITION  OF  THE  URINE 

The  urine  removes  the  soluble  products  of  metabolism 
from  the  organism  and  the  respiration  eliminates  the  gaseous 
products.  The  two  mechanisms  combined  maintain  the 
normal  reaction  of  the  blood. 

In  general,  the  organic  constituents  of  the  urine  comprise 
compounds  which  contain  nitrogen.  Dakin,2  however,  finds 
that  formic  acid,  H.COOH,  is  a  constant  constituent  of  urine 
during  fasting,  and  that  the  quantity  is  considerably  increased 
after  carbohydrate  and  after  fat  ingestion,  to  a  lesser  extent  also 
after  protein  ingestion.  He  interprets  this  as  signifying  that 
all  three  foodstuffs  yield  formic  acid  as  an  end-product  of 
their  metabolisms.  Although  the  production  of  formic  acid 
may  be  considerable,  it  is  so  readily  oxidizable  that  it  is  elimi- 
nated in  only  small  amounts  in  the  urine. 

The  study  of  creatinin  and  creatin  as  excretory  products 
was  stimulated  by  the  discovery  by  Folin  of  a  quick  and 
accurate  method  of  determination. 

He  gave  a  diet  of  milk,  cream,  and  carbohydrate  which 
is  free  from  creatinin  and  the  purin  bases,  and  noted  the 
effect  of  high  and  low  protein  content  of  the  diet  on  the 
composition  of  human  urine. 

One  of  Folin's3  experiments  may  thus  be  tabulated,  per- 
centages being  rendered  in  black  type  (see  Appendix,  p.  573) : 

1  Further  details,  Lusk:  "Archives  of  Internal  Medicine,"  1915,  xv,  939. 

2  Dakin,  Janney,  and  Wakeman:  "Journal  of  Biological  Chemistry,"  1913, 

xiv>  34i- 

3  Folin:   "American  Journal  of  Physiology,     1905,  xin,  117. 


THE  INFLUENCE  OF  PROTEIN  FOOD 


209 


INFLUENCE  OF  HIGH  AND  LOW  PROTEIN  DIETS  ON  THE  RELA- 
TIVE AMOUNTS  OF  THE  NITROGENOUS  CONSTITUENTS 
OF   THE    URINE. 


Food. 

Composition  of  the  Urine  in  Grams. 

In  Grams. 

In  Cal- 
ories. 

Total 
N. 

Urea 

N. 

Ammo- 
nia 

N. 

Uric 
Acid 

N. 

Creatinin 
N. 

Undeter- 
mined 

N. 

Protein,  118  =   10 
N 

2786 

[2153 

16.8 
3-6 

14.70 
87.5% 

2.20 
6i.7% 

O.49 

3.0% 

O.42 

11-3% 

O.18 
1-1% 

O.09 

2.5% 

0.58 
3-6'c 

0.60 
17-2% 

0.85 

A     n.07 

Fat,  148  

Carb.,  225 

Protein,  6  =  1  N  . 
Fat,  K2 

4-9.0 

0.27 

Carb.,  400 

7-3% 

A  study  of  this  table  will  reveal  the  fact  that  if  a  man  ingest 
a  diet  containing  a  medium  amount  of  protein,  and  again  one 
that  is  nearly  free  from  protein,  the  difference  in  the  character 
of  the  urine  in  the  two  cases  is  almost  exclusively  due  to  a 
difference  in  the  output  of  urea.  The  quantity  of  creatinin 
eliminated  remains  independent  of  the  quantity  of  protein 
metabolized,  and  the  same  thing  holds  true,  as  a  rule,  for  uric 
acid  (see  p.  540).  This  led  Folin  to  distinguish  between  an 
endogenous  protein  metabolism  which  resulted  in  the  constant 
and  even  production  of  creatinin  and  was  a  manifestation  of 
cell  metabolism,  and  an  exogenous  protein  metabolism  as  rep- 
resented by  the  urea  elimination  which  is  in  greater  part  de- 
rived from  ingested  protein. 

Creatinin. — McCollum1  has  observed  that  pigs  may  be 
nourished  for  long  periods  of  time  when  fed  with  a  mixture  of 
starch  and  inorganic  salts  in  sufficient  quantity  to  maintain 
their  weights  and  energy  requirements.  After  twenty-one  to 
thirty-six  days  of  this  diet  the  relation  of  creatinin  N  to  total 
N  in  the  urine  is  a  constant,  or  18.5  :  100.  Since  the  crea- 
tinin N  has  this  as  an  invariable  constant  (when  the  diet  is 
free  from  this  constituent)  it  follows  that  the  true  minimal 

1  McCollum:   "American  Journal  of  Physiology,"  1911-12,  xxix,  210. 
14 


2IO  SCIENCE    OF   NUTRITION 

endogenous  level  of  protein  metabolism  may  be  calculated  at 
any  stage  of  the  experiment  by  multiplying  the  quantity  of 
creatinin  N  by  5.5  Nitrogen  in  excess  of  this  is  supposed  to 
be  derived  from  the  destruction  of  ' 'deposit  protein"  (see  p. 
287). 

The  table  just  given,  which  shows  Folin's  urinary  figures 
for  the  seventh  day  of  a  starch-cream  diet  in  man,  shows  a 
relationship  of  17.2  :  100  between  creatinin  N  and  total  N, 
thus  indicating  that  the  principle  may  be  applicable  to 
man. 

The  daily  elimination  of  a  gram  or  more  of  creatinin  in 
the  urine  is  certainly  of  moment. 

Creatinin  continues  to  be  eliminated  after  an  Eck  fistula 
(p.  451)  has  been  established  in  a  dog,1  indicating  that  the  liver 
cannot  be  all  important  in  its  production.  If  creatinin  be 
administered  with  the  food  it  is  almost  completely  elimi- 
nated in  the  urine.2  The  creatinin  elimination  is  not  in- 
fluenced by  muscular  work,3  nor  by  the  increased  metabolism 
of  body  proteins  which  follows  phosphorus-poisoning  in  fast- 
ing dogs.4 

All  of  these  facts  seem  to  indicate  that  there  is  a  mechanism 
in  the  muscles  which  is  constantly  active  preparing  a  def- 
inite quantity  of  creatinin.  Whether  this  comes  from  arginin 
or  not  is  unknown  (see  p.  204). 

Shaffer5  has  proposed  the  term  creatinin  coefficient  to 
represent  the  number  of  milligrams  of  creatinin  nitrogen 
eliminated  per  kilogram  of  body  weight  in  twenty-four  hours. 
He  believes  this  to  be  an  index  of  muscular  development.  In 
37  normal  men  the  creatinin  coefficient  was  between  8  and  11. 
In  full  accord  with  this  theory  Tracy  and  Clark6  find  the 
creatinin  coefficient  of  26  normal  women  students  in  a  profes- 

1  London  and  Boljarski:    "Zeitschr.  fur  physiol.  Chemie,"  1909,  lxii,  465. 
2Folin:   "Hammarsten's  Festschrift,"  1906. 

3  Van  Hoogenhuyze  and  Verploegh :  "Zeitschrift  fur  physiologische  Chemie,'* 
1905,  xlvi,  415. 

4  Lusk:   "American  Journal  of  Physiology,"  1907,  xix,  461. 
6  Shaffer:  Ibid.,  1908,  xxiii,  1. 

6  Tracy  and  Clark:    "Journal  of  Biological  Chemistry,"  1914,  xix,  115. 


THE   INFLUENCE    OF   PROTEIN   FOOD  211 

sional  school  to  average  5.8.  In  two  athletic  women,  with 
unusual  muscular  development  and  control  through  gym- 
nastic exercise,  the  creatinin  coefficients  were  9  and  9.8  or 
the  same  as  in  men. 

Arguing  from  the  premise  that  the  creatinin  metabolism  is 
an  index  of  the  quantity  of  active  protoplasm  of  muscle 
tissue,  Palmer,  Means,  and  Gamble1  have  compared  the  basal 
metabolism  of  8  men  and  9  women  in  relation  to  their  output 
of  creatinin.  The  group  of  men  produced  0.98  calories  of  heat 
per  milligram  of  excreted  creatinin,  and  the  group  of  women 
1.26  calories  for  the  same  unit.  If  the  premise  is  correct,  then 
the  mass  of  active  protoplasm  is  not  a  factor  in  the  measure- 
ment of  the  intensity  of  the  basal  metabolism  (see  p.  130). 

Creatin. — Creatinin  is  the  anhydrid  of  creatin,  a  con- 
stituent of  normal  muscle.  Creatin  by  treatment  with  acid 
is  converted  into  creatinin  as  follows: 

N(CH3) .  CH0CO2H  N(CH3) .  CH2 

/  / 

C  =  NH        +        H20  =  C  =  NH 

\  \ 

NH2  NH C  =  O 

Creatin.  Creatinin. 

The  close  chemical  relation  between  these  two  substances 
has  led  to  a  search  into  the  problem  of  their  physiologic  inter- 
relation, which  as  yet  has  been  crowned  with  small  success. 

Myers  and  Fine2  report  the  following  creatin  content 
of  muscle  in  various  species: 

Man 0.39  per  cent,  creatin. 

Dog 0.37 

Cat 0.45 

Rabbit 0.52 

When  creatin  is  administered  it  may  be  destroyed  or 
eliminated  in  the  urine,  but  it  is  not  eliminated  as  creatinin. 

Calmer,  Means,  and  Gamble:  "Journal  of  Biological  Chemistry,"  1914. 
xix,  239. 

2  Myers  and  Fine:  Ibid.,  1913,  xiv,  9. 


212  SCIENCE    OF   NUTRITION 

Folin1  and  F.  G.  Benedict2  first  reported  the  presence  of 
creatin  in  the  urine  of  fasting  men  and  offered  the  hypothesis 
that  it  arose  from  disintegrating  muscle  tissue.  Cathcart3 
independently  made  the  same  observation,  but  witnessed  the 
disappearance  of  creatin  from  the  urine  of  the  fasting  man 
after  giving  him  carbohydrate,  and  first  suggested  that  carbo- 
hydrate metabolism  was  associated  with  creatin  oxidation. 
Mendel  and  Rose4  reached  the  same  conclusion. 

The  appearance  of  creatin  in. the  urine  in  various  other 
conditions  has  been  attributed  to  the  elimination  of  creatin 
liberated  through  muscle  breakdown,  but  may  now  be  ex- 
plained as  due  to  lack  of  carbohydrate  metabolism.  Among 
the  conditions  reported  in  which  creatin  appears  in  the  urine 
are  phosphorus-poisoning,5  carcinoma  of  the  liver,6  during  the 
period  of  the  involution  of  the  uterus  after  parturition7  and 
also  immediately  before  parturition.8 

However,  Mellanby9  has  shown  that  cesarean  section  with 
removal  of  the  uterus  is  followed  by  the  same  excretion  of 
creatin  as  after  normal  parturition.  Morse10  confirms  these 
observations. 

That  creatin  elimination  is  not  an  index  of  cellular  destruc- 
tion was  beautifully  shown  by  Stanley  Benedict,11  who  main- 
tained a  phlorhizinized  and  fasting  dog  nearly  in  nitrogen  and 
weight  equilibrium  by  feeding  him  with  washed  meat.  The 
results  are  given  below: 

1  Folin:   "Hammarsten's  Festschrift,"  1906. 

2  Benedict,  F.  G.:  Carnegie  Institution  of  Washington,  1907,  Publication 
No.  77,  p.  386. 

3  Cathcart:   "Journal  of  Physiology,"  1007,  xxxv,  500. 

4  Mendel  and  Rose:    "Journal  of  Biological  Chemistry,"  1911-12,  x,  213. 
6Lefmann:  "Zeitschrift  fur  physiologische  Chemie,"  1908,  Ivii,  476. 

6  Van  Hoogenhuyze  and  Verploegh:  Ibid.,  1908,  Ivii,  161.  Also  Mellanby, 
"Journal  of  Physiology,"  1908,  xxxvi,  447. 

7  Shaffer:  "American  Journal  of  Physiology,"  1908,  xxiii,  14. 
8Murlin:    Ibid.,  1909,  xxiii,  p.  xxxi. 

9  Mellanbv.  E.:  Proc.  of  the  Royal  Society,  London,  Series  B,  191 2,  Ixxvi, 
88. 

10  Morse,  A.:    "Journal  of  the  Amer.  Med.  Assoc,"  1915,  Ixv,  1613. 

11  Benedict,  S.  R.,  and  Osterberg:  "Journal  of  Biological  Chemistry,"  1914, 
xviii,  195. 


THE  INFLUENCE  OF  PROTEIN  FOOD 


213 


CREATIN  EXCRETION  IN  A  PHLORHIZINIZED  DOG  IN  N  EQUI- 
LIBRIUM 


Third  day  fasting 

Fourth  day  fast- 
ing: phlorhizin. 

Second  day  phlo- 
rhizin  

Fifth  day  phlo- 
rhizin  


Weight. 


Kg. 
7.62 

7.58 

7-44 

7.08 


N  IN 

Food. 


Grams. 


12.00 
13.46 


N  IN 

Urine. 


Grams. 

2.74 

6-34 
11.91 
12.79 


N  Loss 
From 
Body,     i 


Creatin 

N. 


Grams. 
-2.74 

-6-34 
—  1. 21 
-I.23 


Grams. 
O.075 

O.IIO 

0.154 
0.131 


Cre- 

ATININ 

N. 


Grams. 
O.075 

O.074 

O.071 

O.070 


D  :N. 


3-9 
3-4 

3-2 


On  account  of  the  maintenance  of  the  quantity  of  body 
protein  the  creatinin  excretion  remained  constant,  but  in 
spite  of  this  maintenance  there  was  a  large  elimination  of 
creatin.  At  the  completion  of  the  experiments  analysis  of 
the  muscle-cells  showed  more  rather  than  less  than  the  normal 
content  of  creatin.  These  are  the  only  experiments  which 
demonstrate  an  elimination  of  creatin  without  a  corresponding 
loss  of  body  tissue  or  loss  of  muscle  creatin.  Stanley  Benedict 
concludes  that  the  creatin  elimination  is  due  to  complete  car- 
bohydrate starvation,  that  under  normal  conditions  creatin  is 
probably  formed  in  the  organism  in  relatively  large  amounts, 
and  is  for  the  most  part  utilized  or  destroyed  when  carbo- 
hydrate is  being  oxidized  as  well. 

A  long-continued  carbohydrate  diet  which  is  free  from 
protein  reduces  the  quantity  of  creatin  present  in  muscle 
tissue.1 

Muscular  fatigue  leaves  the  creatin  content  of  dog's 
muscle  unchanged  from  the  normal.2 

Summarizing  the  known  data,  it  appears  that  creatinin  is 
not  oxidized  in  the  organism,  but  if  formed  is  probably  com- 
pletely eliminated  in  the  urine,  whereas  creatin  is  continuously 
produced  in  quantities  above  the  requirement  for  the  satura- 
tion of  muscle  tissue,  and  this  excess  in  the  presence  of  carbo- 

1  Myers  and  Fine:    "Journal  of  Biological  Chemistry,"  1913,  xv,  305. 

2  Mellanby:  "Journal  of  Physiology,"  1908,  xxxvi,  447;  Scaffidi:  "Biochem- 
ische  Zeitschrift,"  1913,  1,  402. 


214  SCIENCE    OF   NUTRITION 

hydrate  oxidation  may  be  destroyed,  but  in  the  case  of  carbo- 
hydrate starvation  may  be  eliminated  in  the  urine. 
Uric  Acid. — See  Chapter  on  Purin  Metabolism. 

THE  REACTION  OF  URINE   AND  BLOOD 

Ammonia. — Friedrich  von  Miiller1  was  the  first  to  affirm 
that  the  number  of  grams  of  ammonia  eliminated  by  an  organ- 
ism during  twenty-four  hours  might  be  used  as  an  indicator  of 
the  intensity  of  acid  formation  within  the  body.  Infection  of 
the  bladder  leading  to  ammoniacal  fermentation  has  sometimes 
caused  erroneous  deductions  to  be  drawn  from  experimental 
data.  Murlin  and  Bailey2  found  that  the  bladder,  especially  in 
women,  could  be  irrigated  to  advantage  with  a  warm  saturated 
solution  of  boric  acid  in  order  to  avoid  this  complication. 

To    understand    the    conditions    under    which    ammonia 

appears  in  the  urine,  one  must  understand  the  mechanism  by 

which  the  blood  is  constantly  held  at  a  point  the  very  slightest 

degree  on  the  alkaline  side  of  neutrality. 

Distilled  water  is  absolutely  neutral  in  reaction,  that  is  to 
+ 
say,  the  number  of  free  H  ions  is  equal  to  the  number  of  free 

hydroxyl  ions  OH.3  A  normal  solution  of  hydrochloric  acid 
contains  i  gram  of  free  hydrogen  ions  in  a  liter  of  water, 
whereas  in  pure  distilled  water  only  one-ten-millionth  of  a  gram 
of  free  hydrogen  ions  is  present.  Solutions  are  acid  which  have 
more  than  one-ten-millionth  of  a  gram  of  hydrogen  ions  in  a 
liter.  They  become  alkaline  when  the  hydrogen  ion  con- 
centration falls  below  this  point,  which  for  convenience  may 
be  written  io-7.  Thus,  when  the  hydrogen  ion  concentra- 
tion is  one  part  in  one  hundred  million  or  io~  the  hydroxyl 
concentration  represents  one-millionth  normal  alkaline  solu- 
tion. The  hydrogen  ion  concentration  of  the  blood  varies  be- 
tween io-7  (which  it  reaches  only  in  severe  acidosis)  and  io-  , 
which  is  attained  only  after  the  administration  of  alkalies. 

1  Miiller:   "von  Leyden's  Handbuch  der  Ernahrungstherapie,"  1903,  i,  261. 

2  Murlin  and  Bailey:  "Archives  of  Internal  Medicine,"  1913,  xii,  288. 

3  Consult  Michaelis:  "Die  Wasserstoffionenkonzentration,"  Berlin,  1914. 


THE  INFLUENCE  OF  PROTEIN  FOOD  215 

The  addition  of  one-millionth  of  a  gram  of  hydrogen  ions 
(which  would  be  contained  in  36.5-millionths  of  a  gram  of 
hydrochloric  acid)  to  a  liter  of  water  would  change  its  hydrogen 
ion  concentration  of  io-7  to  one  of  less  than  io-6.  Some 
cells  cannot  live  in  this  concentration  of  acid. 

In  order  to  abolish  cumbersome  numbers,  such  as  0.35  X  io~ 7, 
Sorensen  suggested  that  the  negative  exponent  be  used  as  a 
whole  number.     This  is  called  the  hydrogen  ion  exponent  or 

N/10  acid  =  10    *  PH  =  1 

N/1,000,000     =  10  PH  =  6 

N/500,000  =  2  X  io-6  PH  =  5.70 

(log.  2  =  0.3;  —  6  +  0.3  =  —  5-7o) 
N/28,580,000  =  0.35   X  io"7  Ph  =  7.45 

The  last  figure  given  above  represents  an  alkaline  solution 
of  three  ten-millionths  normal,  or  the  equivalent  of  0.000012 
grams  of  NaOH  dissolved  in  a  liter  of  water.  This  is  the  usual 
alkalinity  of  the  blood,  and  though  so  slight  that  it  may  almost 
be  called  neutrality  is  yet  of  definite  importance. 

McClendon,1  after  careful  experimentation,  concludes  that 
the  normal  PH  of  venous  blood  is  7.5,  with  a  range  between 
7.45  to  7.55.  The  extreme  difficulty  of  the  technic  renders 
the  reports  of  many  experimenters  only  relatively  accurate. 

The  use  of  logarithms  as  expressive  of  acidity  requires  a 
little  practice  to  accustom  oneself  to  think,  for  example,  that 
PH  =  5.70  represents  a  solution  whose  acidity  is  half  that  rep- 
resented by  PH  =  6.  Also,  it  must  be  remembered  that  the 
smaller  the  figure,  the  higher  the  concentration  of  hydrogen 
ions. 

To  Lawrence  J.  Henderson2  belongs  the  credit  of  the  follow- 
ing analysis:  The  proper  action  of  physiologic  processes  de- 

1  McClendon  and  Magoon:  "Journal  of  Biological  Chemistry,"  1916, 
xxv,  669. 

2  Henderson,  L.  J.:  "Ergebnisse  der  Physiologie,"  1909,  viii,  254;  "Journal 
of  Biological  Chemistry,"  191 1,  ix,  403. 


2l6  ■  SCIENCE   OF   NUTRITION 

pends  on  the  accurate  adjustment  and  preservation  of  temper- 
ature, molecular  concentration,  and  neutrality.  Within  the  or- 
ganism there  is  a  constant  formation  of  acid  substances,  princi- 
pally carbonic,  sulphuric,  and  phosphoric  acids,  which  imme- 
diately combine  either  wholly  or  in  part,  according  to  their 
several  avidities,  with  the  basic  constituents  of  the  protoplasm 
and  blood.  In  pathologic  conditions  /3-oxy  butyric  acid  and 
aceto-acetic  acid  claim  their  share  of  base.  Metabolism,  there- 
fore, operates  to  lower  the  unvarying  alkaline  reaction  of  the 
blood.  This  reaction,  according  to  Henderson,  is  maintained 
under  conditions  in  which  89  per  cent,  of  the  phosphates  of  the 
blood  are  dibasic,  as  in  Na2HP04,  and  1 1  per  cent,  monobasic,  as 
NaH2P04;  and  in  which  93  per  cent,  of  the  carbon  dioxid  is 
present  as  in  NaHC03,  and  7  per  cent,  free  as  free  C02.  Hen- 
derson states  that  the  arrangement  of  these  four  substances 
in  the  blood  is  such  that  the  whole  system  surpasses  in 
efficiency  any  possible  closed  aqueous  solution  of  like  con- 
centration for  preserving  the  hydrogen  ion  concentration  of 
the  blood  at  the  normal  of  0.3  X  10 ~7. 

If  an  acid  be  introduced  into  this  system,  not  only  may 
monosodic  phosphate  be  formed  from  disodic  phosphate  or 
additional  amounts  of  C02  dissociated  from  sodic  bicarbonate, 
but  both  these  acid  substances  maybe  eliminated  by  the  kidney 
and  lungs  respectively,  thereby  maintaining  the  reaction  at  a 
normal  level.  The  high  diffusibility  of  these  acid  products 
assists  in  this  regulation. 

If  alkali  increases  in  the  system,  this  though  converted  into 
bicarbonate  must  necessarily  be  accompanied  by  a  large  in- 
crease in  osmotic  pressure.  The  elimination  of  an  alkaline 
urine  corrects  this. 

Carbonic  acid  is  lost  through  the  lungs  without  loss  of 
alkali  to  the  body. 

Phosphoric  and  sulphuric  acids  are  removed  from  the  blood 
by  the  kidney  in  the  forms  of  NaH2P04  and  Na2S04.  If  they 
were  removed  in  other  forms  the  urine  would  be  intensely 
acid.     The  ordinary  acid  formation  in  the  human  organism 


THE   INFLUENCE    OF   PROTEIN   FOOD  217 

corresponds  to  between  600  and  700  c.c.  of  N/10  acid  solution 
daily.1  On  account  of  the  bases  in  combination  the  actual 
PH  in  222  specimens  of  urines  for  twenty-four  hours  from  16 
individuals  showed  an  average  value  of  5.98,  the  range  being 
between  5.1  to  y.2  For  a  short  period  the  urine  may  be  as 
alkaline  as  7.4.  Blatherwick3  finds  the  average  PH  of  30  urines 
of  vegetarians  to  be  6.63.  The  titratible  acidity  appears  to 
be  a  function  of  the  ionized  hydrogen  present,  and  is  almost 
wholly  due  to  the  excess  of  primary  phosphate  over  secondary 
phosphate. 

The  quantity  of  ammonia,  though  it  presents  a  clear  gain 
of  so  much  alkali  for  the  body,  does  not  appear  to  vary  for 
purposes  of  regulating  the  reaction  of  the  blood.  The  main 
regulation  is  accomplished  by  the  elimination  of  acid  phos- 
phate and  carbon  dioxid.  Only  in  pathologic  conditions  with 
acid  formation  is  ammonia  drawn  upon  for  purposes  of  regu- 
lation. 

The  body's  reserves  of  alkali  are  considerable,  and  re- 
plenishment is  usually  accomplished  through  alkalis  con- 
tained in  the  food  (see  p.  361). 

According  to  Michaelis,4  the  reaction  of  the  fluid  which  may 
be  expressed  from  fresh  tissues  and  thrown  in  boiling  water  to 
prevent  postmortal  acid  formation  is  not  alkaline  like  blood, 
but  is  almost  exactly  neutral. 

Bearing  in  mind  the  fundamental  factors  presented  above, 
one  may  now  consider  the  actual  results  of  administering 
acids  or  alkalies  upon  the  composition  of  the  urine  and  blood. 

In  the  first  place,  it  was  shown  by  Haldane  and  Priestley5 
that  a  very  small  increase  in  the  tension  of  carbon  dioxid  in 
the  alveolar  air  was  accompanied  by  a  stimulation  of  the 
respiratory  center.     Krogh  and  Krogh6  proved  that  the  tension 

1  Henderson,  L.  J.,  and  Palmer:  "Journal  of  Biological  Chemistry,"  1913, 
xiv,  81. 

2  Henderson  and  Palmer: 'Ibid.,  1914,  xvii,  305. 

3  Blatherwick :  Ibid.,  1914,  xvii,  p.  xl. 

4  Michaelis  and  Kramsztyk:   "Biochemische  Zeitschrift,"  1914,  lxii,  180. 

5  Haldane  and  Priestley:    "Journal  of  Physiology,"  1905,  xxxii,  225. 

6  Krogh  and  Krogh:    "Skan.  Archiv  fur  Physiologie,"  1910,  xxiii,  179. 


2l8 


SCIENCE    OF   NUTRITION 


of  carbon  dioxid  in  the  alveoli  closely  follows  that  of  arterial 
blood.  Finally,  Hasselbalch1  showed  that  in  reality  an  in- 
crease in  the  hydrogen  ion  concentration  of  the  blood  was  the 
real  stimulus  to  respiration,  and  thus  caused  the  blood  to  be 
automatically  relieved  of  excess  of  acid  ions  existing  in  the 
form  of  HC03.  In  experiments  he  showed  that  when  an 
acid  urine  was  being  secreted  the  C02  tension  of  the  alveolar 
air  was  lowered,  indicating  increased  acid  in  the  blood.  A 
diet  which  produced  a  less  acid  or  an  alkaline  urine  increased 
the  C02  tension  of  the  alveolar  air,  indicating  a  larger  content 
of  alkali  in  the  blood. 

The  figures  for  one  experiment  may  be  here  reproduced: 


Alveolar  CO2 

Tension  in 

Mm.  Hg. 

PH  of  Blood — 

At  40  Mm.  CO2 
Tension. 

At  Alveolar  CO2 
Tension. 

Meat  diet.  . 

38.9 
43-3 

7-33 
7.42 

7-34 

Vegetarian  diet 

7-36 

In  another  experiment  a  larger  volume  of  respiration  was 
found  to  accompany  the  lower  alveolar  C02  tension,  as  follows: 


Meat  diet 

Vegetarian  diet. 


Alveolar  CO2 

Tension  in 

Mm.  Hg. 


38.5 
43-1 


Alveolar  Ventilation 
Liters  per  Minute 
at  37  Degrees. 


4.40 
4.08 


These  results  demonstrate  that  C02  acts  only  indirectly 
upon  the  respiratory  center.  For  the  maintenance  of  a  con- 
stant reaction  of  the  blood,  more  C02  is  required  in  the  pres- 
ence of  alkali  than  in  the  presence  of  acid.  The  variation  in 
the  ventilation  of  the  lungs,  brought  about  by  the  sensitiveness 
of  the  respiratory  center  to  H  ions  controls  the  C02  tension  in 


1  Hasselbalch :    "Biochemische  Zeitschrift,"  1912,  xlvi,  403. 


THE    INFLUENCE    OF    PROTEIN   FOOD 


2ig 


the  alveoli,  so  that  the  reaction  of  the  blood  remains  practically 
unchanged  under  the  two  given  different  dietary  conditions. 

It  is  only  in  exceptional  cases  that  in  the  normal  life  of  a 
man  at  rest  the  diurnal  variation  in  the  carbon  dioxid  tension 
of  the  alveoli  exceeds  the  equivalent  of  2  mm.  of  mercury.1 

The  administration  of  acid  to  such  an  extent  that  the 
reaction  of  the  blood  becomes  acid  produces  death.  Such 
blood  cannot  combine  with  carbon  dioxid.  Thus,  after 
giving  90  c.c.  of  half-normal  hydrochloric  acid  intravenously 
to  a  dog,  death  resulted  in  virtue  of  the  production  of  an  ex- 
perimental acidosis,  the  PH  equalling  6.9  in  the  blood.2  The 
reduction  of  carbonic  acid  in  the  blood  of  a  rabbit  from  45 
volumes  per  cent,  to  10. 1  per  cent.,  with  accompanying 
dyspnea,  was  observed  by  Loewy  and  Miinzer3  after  the 
administration  of  0.72  gram  of  hydrochloric  acid  per  kilogram 
of  body  weight,  and  Porges4  has  noted  that  intravenous  in- 
jection of  monosodic  phosphate  into  a  narcotized  rabbit 
raises  the  respiratory  quotient  from  0.68  to  0.79,  indicating  the 
elimination  of  carbon  dioxid  from  the  plasma. 

If,  however,  acid  in  moderate  quantity  is  given  with  food, 
increased  ammonia  production  may  neutralize  the  acid  given. 

This  has  been  beautifully  shown  with  calves,5  as  appears  in 
the  following  experiment: 

CALF:  WEIGHT,  100  KG.;    FOOD,  9.1  KG.  OF  MILK  DAILY 


Period. 

No.  OF 
Days. 

N  IN 

Food. 

N  IN 

Urine. 

Per  Cent. 

NNa— N. 

Per  Cent. 
Urea  N. 

No  acid  given 

9 

6 

7 
3 

Grams. 
30.00 
30.00 
30.00 
30.00 

Grams. 

12.4 
12.4 

"•5 

12.9 

12.8 
19.4 
31-7 
37-o 

76.0 
74.1 
55-8 
43-i 

220  c.c.  normal  HC1 

330  c.c.  normal  HC1 

500  c.c.  normal  HC1 

1  Erdt:  "Deutscbes   Archiv  fur  klinische  Medizin,"  1915,  cxvii,  497;  Hig- 
gins,  "American  Journal  of  Physiology,"  1914,  xxxiv,  114. 

2  Levy,  Rowntree,  and  Marriott:    "Archives  of  Internal  Medicine,"  1915, 
xvi,  389. 

3  Loewy  and  Miinzer:    "Archiv  fur  Physiologie,"  1901,  81. 

4  Porges:   "Biochemische  Zeitschrift,"  1912,  xlvi,  1. 

5  Steenbock,  Nelson,  and  Hart:    "Journal  of  Biological  Chemistry,"  1914, 
xix,  399. 


220 


SCIENCE    OF   NUTRITION 


Only  when  the  larger  quantities  of  acid  were  administered 
did  it  appear  that  the  bones  were  attacked,  and  this  was  at  the 
expense  of  their  calcium  carbonate  content.  The  administra- 
tion of  acid  did  not  prevent  the  growth  and  development  of 
the  calf. 

In  man  hydrochloric  acid  may  be  given  with  a  similar 
protective  rise  of  ammonia,  as  appears  below:1 


CONSEQUENCE    OF 
DIET 

ADDING    HYDROCHLORIC    ACID    TO    THE 
OF  MAN.     DAILY   AVERAGES 

No.  OF 
Days. 

Alveolar  Tension 
Per  Cent. 

Urine. 

CO2. 

O2. 

N. 

NH3. 

P206. 

CI. 

Normal  diet.  .  . 
Same  +  HC1.  . 

3 

3 

6.00 

5-98 

5.IO 

5-36 

Grams. 

I3-50 
I3-6S 

Grams. 
O.92 
1-59 

Grams. 
I.92 
2-15 

Grams. 
4.28 
7.92 

In  the  above  experiment  85  c.c.  of  a  solution  containing 
12  per  cent,  or  10.2  grams  of  chlorin  was  added  to  the  food 
during  three  days,  being  an  average  of  3.4  grams  of  chlorin  per 
day.  This  would  require  1.6  grams  of  ammonia  to  effect  its 
neutralization.  On  the  third  day  of  acid  administration  the 
ammonia  rose  to  an  output  of  2.03  grams.  The  phosphates 
increased  12  per  cent,  and  there  was  a  rise  in  the  acidity  of  the 
urine.  As  the  result  of  these  protective  agencies  the  carbon 
dioxid  tension  in  the  blood  remained  unchanged  after  the 
administration  of  hydrochloric  acid. 

In  certain  pathologic  states,  such  as  diabetes,  phosphorus- 
poisoning,  nephritis  in  some  of  its  forms,  the  so-called  food 
intoxication  of  infants,2  and  other  conditions,  there  is  an  in- 
creased production  of  ammonia  in  the  body  for  the  neutraliza- 
tion of  acids  of  endogenous  origin.  This  may  be  accompanied 
by  a  withdrawal  of  body  alkali,  so  that  the  power  to  combine 

1  Begun,  Herrmann,  and  Miinzer:    "Biochemische  Zeitschrift,"  1915,  bod, 

255- 

2Howland  and  Marriott:  "American  Journal  of  Diseases  of  Children," 
1916,  xi,  309. 


THE  INFLUENCE  OF  PROTEIN  FOOD  221 

with  carbon  dioxid  is  greatly  reduced  and  the  alveolar  tension 
of  C02  falls  in  consequence.  However,  even  under  these 
conditions  the  reaction  of  the  blood  may  remain  unaffected. 
This  is  strikingly  illustrated  in  the  experiments  of  Poulton1  on 
cases  suffering  from  severe  diabetes,  in  which  condition  /3-oxy- 
butyric  acid  is  largely  formed.    (See  table,  p.  468.) 

The  blood  of  the  first  six  patients  showed  a  normal  PH. 
Only  in  the  depth  of  coma  a  few  hours  before  death  is  there  a 
distinct  fall  in  alkalinity,  and,  indeed,  this  fall  may  not  be  as 
great  as  in  a  normal  person  after  climbing  a  thousand  feet  in 
twenty-five  minutes,  under  which  circumstances  the  PH  may 
be  7.09  (see  p.  322). 

It  is  evident  that  the  reaction  of  the  blood  in  severe 
diabetes  is  maintained  at  the  normal  through  the  reduction  of 
its  carbon  dioxid  content.  Such  a  reduction  in  carbon  dioxid 
combining  power  indicates  a  reduction  in  the  alkali  reserve 
of  the  blood,  and  forms  the  basis  of  the  important  method  of 
Van  Slyke  for  investigating  the  intensity  of  acidosis. 

That  ammonia  in  the  urine  is  an  indicator  of  acid  formation 
and  not  due  to  a  pathologic  disturbance  of  urea  formation 
was  shown  by  Muenzer,2  who  gave  alkali  in  cirrhosis  of  the  liver 
and  reduced  the  quantity  of  ammonia  elimination  to  normal. 
Fiske  and  Karsner3  find  that  livers  which  have  been  severely 
damaged  in  the  living  animal  by  administration  of  chloroform, 
phosphorus,  hemolytic  immune  sera,  hydrazin  sulphate,  or 
phlorhizin  still  preserve  the  power  of  transforming  perfused 
ammonium  carbonate  into  urea.  Janney,4  in  von  Miiller's 
laboratory,  gave  bicarbonate  of  sodium  to  men  and  found  that 
the  quantity  of  ammonia  in  the  urine  was  reduced  to  almost 
undeterminable  traces;  hence  the  ammonia  in  the  urine  has 
as  its  sole  function  the  neutralization  of  acid  bodies  and 
ceases  to  be  formed  in  the  presence  of  an  excess  of  fixed  alkali. 

1  Poulton:  Proceedings  of  the  Physiological  Society,  p.  i;  "Journal  of  Phys- 
iology," 191 5,  1. 

2  Muenzer:    "Deutsches  Archiv.  fur  klin.  Med.,"  1804,  lii,  199  and  417. 

3  Fiske  and  Karsner:    "Journal  of  Biological  Chemistry,"  1914,  xviii,  381. 

4  Janney:   "Zeitschrift  fur  physiologische  Chemie,"  1911-12,  lxxvi,  99. 


222  .  SCIENCE   OF   NUTRITION 

Howland  and  Marriott1  find  that  the  administration  of 
acid  phosphates  causes  no  increase  in  ammonia  in  the  urine. 

Klein  and  Moritz2  found  that  on  the  day  following  a  diet 
which  was  rich  in  fat  there  was  an  increase  in  the  quantity  of 
fixed  alkali  in  the  urine  and  a  corresponding  fall  in  the  quantity 
of  ammonia.  They  interpret  the  results  as  signifying  that 
the  alkali  was  temporarily  involved  in  fat  metabolism  (for- 
mation of  soaps)  and  was  eliminated  when  this  need  was  no 
longer  present. 

The  consideration  of  the  ingestion  of  alkalies  and  bases  in 
the  food  will  be  discussed  in  the  chapter  on  A  Normal  Diet. 

1  Howland  and  Marriott :  Reported  at  the  meeting  of  the  American  Phys- 
iological Society,  December,  191 6. 

2  Klein  and  Moritz:   "Deutsches  Archiv  fur  klin.  Med.,"  1010,  xcix,  162. 


CHAPTER  VII 
THE  INFLUENCE  OF  PROTEIN  FOOD    (Concluded) 

PART    III— THE    RESPIRATORY    METABOLISM 

The  discussion  of  the  more  important  details  of  the  break- 
down of  amino-acids  in  the  organism  reveals  the  modern 
beginning  of  mental  penetration  into  the  biochemical  reactions 
in  the  organism. 

The  gross  results  of  protein  ingestion  are  to  be  ascertained 
by  other  means,  by  a  study  of  the  respiratory  metabolism  and 
by  calorimeter  observations. 

Bidder  and  Schmidt1  gave  meat  to  the  full  extent  of  its 
appetite  to  a  cat  which  had  previously  been  starved  and 
reported  the  following  figures  for  the  respiratory  exchange: 

co2  o2 

Grams.  Grams. 

Fasting _ _ 53.52  50.18 

Excessive  meat  ingestion 1 13.52  103.84 

Many  subsequent  experiments  have  brought  to  light  this 
characteristic  increase  in  metabolism  after  the  ingestion  of 
protein  in  excess. 

In  1862  Pettenkofer  and  Voit  (see  p.  155)  noted  that  after 
giving  meat  in  large  quantity  a  portion  of  the  carbon  of  the 
protein  metabolized  was  retained  in  the  body,  which  they  in- 
terpreted as  indicating  a  production  of  fat  from  protein. 
Frank  and  Trommsdorff2  and  also  Rubner3  gave  meat  in  large 
amount  to  dogs,  and  determined  the  carbonic  acid  output  of 
the  animals  during  intervals  lasting  between  three  to  six  hours. 

1  Bidder  and  Schmidt:   "Verdauungssafte  und  Stoffwechsel,"  1852,  p.  356. 

2  Frank  and  Trommsdorff:    "Zeitschrift  fur  Biologie,"  1902,  xliii,  266. 

3  Rubner:  "Gesetze  des  Energieverbrauchs,"  1902,  p.  365. 

223 


224 


SCIENCE    OF   NUTRITION 


The  first  named  authors  noted  that  although  the  urinary- 
nitrogen  elimination  showed  a  maximum  rise  of  nearly  eight 
times  that  of  fasting  and  varied  greatly,  the  carbonic  acid 
elimination  was  not  so  largely  increased  and  was  much  more 
even. 

The  details  of  the  results  following  the  ingestion  of  large 
quantities  of  meat  by  a  dog  are  to  be  found  in  the  calorimetric 
observations  of  Williams,  Riche,  and  Lusk.1  These  authors 
made  observations  in  hourly  periods  upon  the  nitrogen  in  the 
urine,  the  carbonic  acid  elimination  and  oxygen  absorption, 
and  the  heat  production  of  a  dog  following  the  ingestion  of 
1 200  grams  of  meat.  The  results  are  in  part  presented  in  the 
accompanying  curve: 


85  R.Q. 

.80 
75 

40  Calorics 

35 

30 

25 


2D  6ms. 
N. 
15 


/ 


/ 


■N. 


22  23  0    I    2    3    4    5    0    7    8   9    10  11    12  13  14  15  16  17  18  19  20  21 
HOURS  AFTER  1200  6RAMS  MEAT 


Fig.  15. — Showing  the  R.  Q.,  the  total  metabolism  determined  by  indirect 
(heavy  black  line)  and  direct  (broken  line)  calorimetry,  as  well  as  the  nitrogen 
elimination  (dotted  line),  during  hourly  periods  after  the  ingestion  of  1200  grams 
of  meat. 

1  Williams,  Riche,  and  Lusk:  "Journal  of  Biological  Chemistry,"  1912,  xii, 
349- 


THE  INFLUENCE  OF  PROTEIN  FOOD  225 

During  the  fourth  hour  the  nitrogen  in  the  urine  reached 
a  level  of  1.80  grams  and  remained  between  1.76  and  2  grams 
per  hour  during  a  period  of  eleven  hours.  During  this  period 
the  heat  production  was  nearly  twice  the  normal  basal  metab- 
olism, and  the  increase  was  proportional  to  the  increase  in  pro- 
tein metabolized  as  calculated  from  the  increased  nitrogen  elim- 
ination above  that  of  the  basal  metabolism.  However,  during 
the  second  and  third  hours,  in  which  the  increase  in  heat 
production  almost  reached  its  maximum,  the  urinary  nitrogen 
was  only  0.89  and  1.55  grams  respectively.  This  is  due  to 
the  fact  that  urea  was  accumulating  in  the  blood  and  the 
quantity  of  its  elimination  in  the  urine  did  not  at  first  truly 
represent  the  intensity  of  the  metabolism  of  protein  (see  p.  1 73) . 
This  fact  is  made  certain  by  the  curve  of  glucose  and  nitrogen 
elimination  obtained  by  Janney1  after  giving  serum  albumin 
to  a  phlorhizinized  dog  (see  p.  243).  In  this  curve  the  glucose 
elimination  reached  its  maximum  during  the  first  hour,  the 
nitrogen  elimination  during  the  fifth.  It  seems  also  probable 
that  after  giving  1200  grams  of  meat  to  the  normal  dog 
the  establishment  of  a  plateau  of  even  nitrogen  elimination 
indicates  that  during  this  period  the  influx  of  protein  nitrogen 
from  the  intestine  equalled  its  destruction  within  the  cells  and 
its  outgo  through  the  urine.  When  a  fall  in  the  nitrogen 
output  set  in,  the  metabolism  also  fell  as  the  result  of  the  de- 
crease in  protein  metabolism. 

During  an  experimental  period  of  twenty-two  hours  the 
heat  production  calculated  from  the  excreta  was  738.5  calories, 
and  directly  measured  by  the  calorimeter  was  718.5  calories, 
a  difference  of  20  calories,  or  2.7  percent.  During  the  first 
two  experimental  hours  there  was  always  a  considerable 
discrepancy  between  indirect  and  direct  calorimetry.  It  is 
now  certain  that  this  was  due  to  the  fact  that  the  meat  was 
given  when  cold  (see  p.  123).  Allowing  for  this  error,  the 
indirect  and  direct  methods  agree  within  less  than  2  per  cent. 

An  interesting  fact  revealed  in  the  analysis  of  the  respira- 

1  Janney:    "Journal  of  Biological  Chemistry,"  1915,  xx,  329. 
15 


226 


SCIENCE    OF   NUTRITION 


tory  exchange  is  that,  beginning  with  the  second  hour  and 
continuing  for  fourteen  hours  after  the  ingestion  of  protein, 
the  respiratory  carbon  dioxid  is  less  than  that  which  one  would 
expect  if  all  parts  of  the  protein  complex  were  oxidized. 
There  is,  therefore,  carbon  retention  during  this  period.  Such 
carbon  might  have  been  retained  in  the  form  of  carbohydrate 
or  of  fat.  Schreuer1  gave  900  and  1500  grams  of  meat  to  a 
dog  and  determined  the  metabolism  by  the  Zuntz  method 
from  three  to  four  hours  after  meat  ingestion.  He  concluded 
from  the  respiratory  quotient  that  carbon  derived  from  protein 
was  retained  in  the  form  of  carbohydrate.  New  confirmation 
of  the  conversion  of  part  of  the  protein  molecule  into  glucose 
was  afforded  by  the  oxygen  absorption  of  the  dog  of  Williams, 
Riche,  and  Lusk  during  various  periods  following  the  ingestion 
of  1200  grams  of  meat.     These  facts  are  here  set  forth: 

TABLE  CONTRASTING  THE  ACTUAL  OXYGEN  INTAKE  WITH 
THAT  REQUIRED  BY  THEORY  IF  THE  CARBON  RETENTION 
HAD  BEEN  IN  THE  FORM  OF  GLYCOGEN  OR  OF  FAT.  1200 
GRAMS  MEAT  INGESTED  AT  NOON. 


Calories. 

c 

02 

02 

Retained 

02 

(Retained 

(CRe- 

(Calc.  as 

Actual. 

as  Glu- 

tained as 

Found. 

Calculated. 

Glucose). 

cose). 

Fat). 

P.  M. 
I.4.S-     2.45.   . 

38.92 

41.70 

O.IO 

I3-63 

12.99 

12.95 

2-45-  3-45- • 

40.40 

41.29 

i-93 

13.29 

12.56 

"•73 

3.45-  6.45.  . 

121.91 

124.82 

7.86 

43-25* 

40.61 

37-23 

6.45-  9-45- 

122. 11 

122.86 

7.86 

40.35 

40.01 

36.63 

9.45-12.45-  • 

106.70 

III. 67 

7-5° 

35-47 

36.41 

33-19 

12.45-  1.45.  . 

35-86 

36.82 

3-42 

n-34 

12.13 

10.66 

1-45-  2-45-  • 

27.71 

29.32 

2-75 

9-3i 

9-65 

8.47 

2-45-  3-45-  • 

64.24 

62.36 

3.08 

19.56 

20.19 

18.87 

557-85 

570.84 

34-5° 

186.20 

184.55 

169.73 

Dif.  =  2.v 

5  per  cent. 

Dif.  =  o.c 

)  per  cent. 

Dif.=io% 

34.5  grams  glucose  :  28.3  grams  N  :  :  1.2  :  1 

*  Small  leak  in  the  apparatus  during  this  period  determined  the  day  fol- 
lowing to  amount  to  about  1  gram  O2  per  hour. 


The  respiratory  quotients  (see  Fig.   15)   fall  during  the 
hours  of  carbon  retention   to  below   that  of  protein  itself 

1  Schreuer:   "Pfliiger's  Archiv,"  1905,  ex,  227. 


THE  INFLUENCE  OF  PROTEIN  FOOD 


227 


(which  is  0.80),  because  the  unoxidized  carbohydrate  is  re- 
tained in  the  organism  as  glycogen.  If  the  carbon  were 
retained  in  the  organism  as  fat,  the  respiratory  quotient 
would  rise.  If  one  considers  the  period  between  the  hours  of 
6.45  to  9.45  p.  m.,  one  obtains  the  following  picture  of  what 
occurs: 


METABOLISM  OF  A  DOG  DURING  A  THREE-HOUR  PERIOD  OF 
MAXIMAL  PROTEIN  CARBON  RETENTION  AFTER  1200  GRAMS 
MEAT. 


Direct. 

Indirect. 
(C  Retained  =  3.14  Grams.) 

If  Retained 
as  Glucose. 

If  Retained 
as  Fat. 

Calories 

Oxygen,  grams 

Respiratory  quotient. 

122. 11 

40.35 
0.77 

122.86 
40.01 

0.77 

II3-32 

36.63 

O.85 

It  is  obvious  from  these  figures  that  the  oxygen  absorption 
and  the  heat  production  prove  the  retention  of  carbon  either  in 
the  form  of  glucose  or  glycogen  in  the  organism.  During  the 
fourteen  hours  of  carbon  retention  following  the  ingestion  of 
1200  grams  of  meat,  the  actual  oxygen  absorption  was  186.2 
grams  against  a  value  of  184.5,  calculated  on  the  assumption 
that  carbon  was  stored  as  glycogen  or  a  difference  of  0.9  per 
cent.  If  the  carbon  had  been  retained  as  fat,  169.7  grams  of 
oxygen  would  have  been  required,  or  10  per  cent.  less. 

During  these  fourteen  hours  34.5  grams  of  glucose  were 
stored  as  glycogen  in  the  organism  and  28.3  grams  of  N  were 
eliminated  in  the  urine.  This  yields  a  D  :  N  ratio  of  1.2  :  1. 
Since  3.6  is  the  maximum  yield  of  glucose  per  gram  of  N  in 
diabetic  urine,  it  is  evident  that  one-third  of  the  glucose 
derivable  from  protein  in  metabolism  was  retained  in  the 
organism  and  deposited  in  the  liver  and  other  glycogen 
reservoirs.  This  represents  20  per  cent,  of  the  total  energy 
contained  in  the  protein  metabolized. 


2  28  SCIENCE    OF   NUTRITION 

The  production  of  glucose  from  protein  is  not  an  emer- 
gency process  as  some  writers  maintain,  but  it  is  a  normal 
function. 

A  question  which  has  aroused  great  interest  is  that  con- 
cerning the  production  of  fat  from  protein.  Pettenkofer  and 
Voit1  found  that  after  ingesting  considerable  quantities  of 
protein,  although  the  nitrogen  of  the  protein  was  eliminated  in 
the  urine,  a  part  of  the  carbon  was  retained  in  the  body  and 
not  excreted  by  the  usual  channels.  They  estimated  that 
meat  protein  contained  3.68  grams  of  carbon  to  each  gram  of 
nitrogen.  If  less  than  3.68  grams  of  carbon  appeared  in  the 
total  excreta  when  1  gram  of  nitrogen  was  eliminated,  then 
some  protein  carbon  must  have  been  stored  in  the  body. 
This  carbon  might  have  been  retained  in  two  forms — as 
glycogen  or  as  fat.  Claude  Bernard  had  shown  that  glycogen 
increases  in  the  liver  after  the  ingestion  of  protein.  The 
retained  carbon  as  observed  by  Pettenkofer  and  Voit  was  in 
such  large  quantity  as  to  preclude  the  possibility  of  its  re- 
tention entirely  as  glycogen,  and  therefore  they  concluded 
that  fat  must  have  been  prepared  from  protein  and  stored 
up  in  the  body.  This  afforded  an  experimental  basis  for 
the  theory  of  a  production  of  fat  from  protein  in  fatty  de- 
generation. 

Later  Rubner,2  in  Voit's  laboratory,  showed  that  the 
relation  3.68  C  :  1  N  in  protein,  as  used  by  Pettenkofer  and 
Voit,  was  inaccurate,  and  that  meat  fully  extracted  with  ether 
contains  only  3.28  of  carbon  to  one  of  nitrogen  (see  p.  39). 
The  polemical  arraignment  by  Pfliiger3  of  Voit's  older  work 
was  based  upon  these  results  of  Rubner.  Instead  of  there 
being  a  great  retention  of  protein  carbon,  there  was  none 
in  some  experiments  and  very  little  in  others.  The  formation 
of  fat  from  protein  was  evidently  less  easy  of  demonstration 
than  it  had  seemed. 

1  Pettenkofer  and  Voit:  "Annalen  der  Chemie  und  Pharm.,"  1862,  II 
Supplement,  pp.  52  and  361;  "Zeitschrift  fur  Biologie,"  1871,  vii,  433. 

2  Rubner:   Ibid.,  1S85,  xxi,  324. 

3  Pfliiger:    "Pfliiger's  Archiv,"  1892,  Hi,  239. 


THE  INFLUENCE  OF  PROTEIN  FOOD  229 

The  subject  was  investigated  anew  by  Cremer,1  who 
starved  a  cat  for  many  days,  and  then  gave  the  animal  all 
the  lean  meat  it  would  eat,  or  about  450  grams  a  day.  The 
cat  was  kept  in  a  respiration  apparatus  and  the  total  excreta 
were  collected.  The  carbon  belonging  to  the  meat  ingested 
was  calculated  at  the  low  ratio  of  3.18  to  1  of  nitrogen.  The 
average  daily  metabolism  during  the  eight  days  of  meat  in- 
gestion is  indicated  in  the  following  table : 


N  in  urine 

and  feces, 

13.0 

Urine, 
7-5 

Weights  in  Grams 

C  in 

Feces,         Respiration, 
1.4                   25.4 

Meat  C  calcu-  C  from  meat 
lated  from     added  to  the 
N  excreted,          body, 
41.6                  7.3 

34-3 


There  was  a  daily  excretion  of  13  grams  of  nitrogen  corre- 
sponding to  the  liberation  of  41.6  grams  (13  X  3. 18)  of  protein 
carbon.  But  only  34.3  grams  of  carbon  were  actually  elimin- 
ated from  the  body,  and  a  difference  of  7.3  grams  was  re- 
tained in  the  body;  17.5  per  cent,  of  the  protein  carbon  there- 
fore was  not  eliminated.  For  eight  days  the  whole  carbon 
retention  was  58  grams,  which  corresponds  to  a  glycogen 
production  of  130  grams.  The  cat,  however,  contained  only 
35  grams  of  glycogen,  determined  after  killing  it  at  the  end  of 
the  experiment.  The  balance  of  the  carbon  must  have  been 
stored  as  fat. 

Cremer2  notes  that  a  cat  fed  as  above  contains  1 .47  per  cent, 
of  muscle  glycogen,  which  is  as  much  as  the  maximum  (1.37 
per  cent.)  found  by  E.  Voit  in  geese  after  the  ingestion  of 
starch.  One  should  here  recall  that  Pfliiger  (see  p.  175)  found 
as  much  as  10  per  cent,  of  glycogen  in  the  liver  of  a  previously 
fasting  dog  after  it  had  been  fed  with  codfish.  This  is  as 
much  glycogen  as  would  have  been  deposited  after  carbohy- 
drate ingestion. 

1  Cremer:   "Zeitschrift  fur  Biologie,"  1899,  xxxviii,  309. 

2  Cremer:  Ibid.,  1899,  xxxviii,  313. 


230  SCIENCE    OF   NUTRITION 

Since  it  is  known  that  sugar  in  excess  may  be  converted  into 
body  fat  and  that  meat  may  yield  58  per  cent,  of  sugar  in 
metabolism,  there  is  every  reason  to  believe  that  if  protein  be 
ingested  in  excess  the  deaminized  residues  of  many  of  the 
amino-acids  may  be  converted  into  glycogen,  and  then,  if 
this  pathway  be  closed  through  saturation  of  the  body-cells 
with  glycogen,  fat  is  formed  instead  (see  p.  304). 

It  is  quite  possible  that  the  origin  of  fat  from  protein  is  in 
its  nature  the  same  as  the  origin  of  fat  from  carbohydrates. 

In  the  first  edition  of  this  work  (1906,  p.  123)  it  was  com- 
puted from  the  investigations  of  Cremer  with  the  cat  and  from 
those  of  Rubner  with  a  dog  that  40  per  cent,  of  the  protein 
carbon  which  was  capable  of  conversion  into  glucose  could  be 
retained  in  the  organism  either  as  glucose  or  as  fat.  This 
is  to  be  compared  with  33  per  cent,  of  such  glucose  retention 
indirectly  measured  by  Williams,  Riche,  and  Lusk. 

An  interesting  contribution  to  the  subject  of  the  possible 
formation  of  fat  from  protein  has  been  made  by  Weinland,1 
who  found  in  the  case  of  the  blow-fly  (calliphora),  which 
lays  its  eggs  in  meat,  that  both  the  larvae  and  a  pulp  made 
by  crushing  them  had  the  power,  in  the  absence  of  oxygen,  to 
split  peptone  into  amino-acids,  deaminize  these  with  evolution 
of  ammonia,  and  then  with  evolution  of  carbon  dioxid  to 
produce  higher  fatty  acids,  presumably  through  synthetic 
union  of  fragments  of  the  acids  which  had  been  freed  of  their 
amino  groups.  Such  a  procedure  reasonably  explains  the 
formation  of  fat  from  protein  in  the  sense  of  the  older  theories 
(see  p.  171). 

The  question  of  a  "fatty  degeneration"  of  protein  under 
pathologic  conditions  is  another  matter  and  will  be  consid- 
ered in  another  place.     (See  Chapter  XVI.) 

The  experiments  already  described  bring  to  light  a  very 
striking  change  in  the  metabolism  after  the  ingestion  of  protein 
in  excess.  The  total  heat  production  is  markedly  increased. 
To  what  may  this  be  due? 

1  Weinland:   "Zeitschrift  fur  Biologie,"  1908,  li,  197. 


THE  INFLUENCE  OF  PROTEIN  FOOD  23 1 

Von  Mering  and  Zuntz1  believed  that  such  increased 
metabolism  was  due  to  the  activity  of  the  intestinal  tract 
after  the  ingestion  of  food. 

Voit2  criticised  this  view,  and  said  that  a  rise  in  the  carbon 
dioxid  excretion  from  366  grams  in  starvation  to  783  grams 
after  ingestion  of  2500  grams  of  meat  by  a  dog  (see  p.  155)  was 
too  great  to  be  due  to  intestinal  activity,  and,  indeed,  cor- 
responded to  the  rise  noted  only  after  the  hardest  exercise. 
Furthermore,  Voit  had  shown  that  after  giving  a  medium 
quantity  of  fat,  the  carbon  dioxid  excretion  and  oxygen 
absorption  were  almost  the  same  as  in  hunger,  notwithstanding 
the  activity  of  the  filled  intestine.3 

This  question  has  received  very  painstaking  and  elaborate 
investigation  at  the  hands  of  Rubner,  who  has  published  his 
results  in  a  book  entitled  "Die  Gesetze  des  Energieverbrauchs 
bei  der  Ernahrung."  This  volume  is  an  extension  of  a  work  of 
which  a  preliminary  communication  was  published  by  Rubner4 
from  Voit's  Munich  laboratory  in  1885. 

Rubner  shows  that  bones  given  to  a  dog  will  not  increase 
his  metabolism  in  spite  of  the  intestinal  irritation,  so  the 
increase  after  meat  ingestion  is  not  due  to  a  nerve  reflex  of 
mechanical  nature.  Further,  the  metabolism  is  not  raised 
after  the  ingestion  of  meat  extract,  so  the  chemical  stimulus  of 
flavors  which  start  activity  in  the  glands  does  not  affect  total 
metabolism.  Again,  the  ingestion  of  water  in  the  quantity 
contained  in  meat,  while  it  may  cause  a  rise  in  nitrogen  in  the 
urine  followed  by  a  fall — the  rise  being  due  to  a  rapid  washing 
out  of  nitrogenous  decomposition  products — does  not  alter 
the  total  metabolism  in  any  way. 

Lusk5  has  shown  that  urea  when  given  in  the  quantity 
which  would  be  liberated  from  considerable  amounts  of  meat, 

1  von  Mering  and  Zuntz:   "Pfliiger's  Archiv,"  1877,  xv,  634. 

2  Voit:   "Physiologie  des  Stoffwechsels,"  1881,  p.  209. 

3  Compare  also  Benedict,  F.  G.,  and  Pratt:  "Journal  of  Biological  Chem- 
istry," 1913,  xv,  1. 

4  Rubner:  "Sitzungsberichte  d.  kgl.  bayr.  Acad.  d.  Wissenschaft,"  1885, 
Heft  4. 

5  Lusk:    "Journal  of  Biological  Chemistry,"  1912,  xiii,  27. 


232  SCIENCE   OF   NUTRITION 

and  sodium  chlorid,  the  ingestion  of  which  might  induce 
osmotic  exchanges  in  the  cells,  have  no  effect  upon  the  heat 
production. 

Benedict  and  Emmes1  have  demonstrated  that  cathartics 
and  agar-agar  when  given  to  man  have  no  effect  upon  total 
heat  production  in  spite  of  the  intestinal  activity  which  they 
produce. 

The  absence  of  true  "intestinal  work"  or  "Darmarbeit"  in 
the  sense  of  Zuntz  is  further  shown  by  the  fact  that  Johansson2 
has  given  a  fasting  man  75  grams  of  glucose  without  the 
slightest  increase  in  the  output  of  carbon  dioxid.  If  glucose 
had  been  consumed  the  carbon  dioxid  excretion  would  have 
risen  (see  p.  289),  therefore  glucose  was  retained  as  glycogen. 
Since  all  these  processes  were  without  effect  on  the  carbon 
dioxid  output,  it  follows  that  the  intestinal  activities  involved 
did  not  cause  an  increase  in  the  total  metabolism.  Of  similar 
import  are  the  results  by  the  same  writer  after  administering 
50  grams  of  glucose  to  a  diabetic.  The  sugar  was  absorbed 
and  eliminated  in  the  urine  without  affecting  the  carbon 
dioxid  output. 

The  increase  in  metabolism  is  greater  in  the  case  of  protein 
than  with  any  other  food-stuff.  Rubner  calls  this  action  of 
abundant  protein  food  in  raising  the  metabolism  the  specific 
dynamic  action  of  protein.  Rubner  found  that  when  dogs 
were  fed  with  meat  their  bodies  metabolized  in  largely  in- 
creased measure  without  doing  any  external  work.  A  more 
rapid  respiration. alone  betokened  the  increased  oxidation  and 
the  effort  of  the  body  to  rid  itself  of  excess  of  heat  through 
physical  regulation.  The  temperature  of  the  dogs  scarcely 
changed,  so  perfect  is  the  regulatory  mechanism  for  the 
discharge  of  heat.  Thus  in  one  dog  the  temperature  was 
38.160  before  the  meal,  38. 74°  during  the  digestion,  and  38. 170 
at  the  end  of  digestion. 

If  a  large  quantity  of  protein  be  ingested  day  after  day, 

Benedict,  F.  G.,  and  Emmes:  "American  Journal  of  Physiology,"  1912, 
xxx,  197.  2  Johansson:   "Skan.  Archiv  fiir  Physiologie,"  1909,  xxi,  1. 


THE  INFLUENCE  OF  PROTEIN  FOOD  233 

then  the  usual  specific  dynamic  action  occurs  and  also  a 
continued  "secondary"  rise  in  total  day-to-day  metabolism, 
which  increases  with  the  continual  increase  in  protein  metab- 
olism. When  nitrogen  equilibrium  is  established  the  heat 
production  remains  constant  at  a  higher  level. 

Rubner1  illustrates  this  important  fact  in  the  following 
experiment  on  a  dog,  the  food  of  which  contained  17  grams 
of  nitrogen: 

Calories  in  Total  Calories  of 

Meat  Ingested.  N  to  Body.         Carbon  to  Body.         Metabolism. 

o     — 1.31  310.61 

o     — 1.52  ....  278.00 

481.5 3-95  2-97  3H-43 

481. S 2.80  3-70  333-82 

481.5 2.30  1. 61  368.41 

481.5 2.20  2.53  361.70 

481.5 °-92  4-45  375-47 

481.5 0.20  4-3i  395-77 

o    -3-7o  ....  357-20 

0    -2.64  310.29 

This  experiment  of  Rubner  shows  that  the  amount  of 
protein  carbon  retained  in  the  body  for  the  production  of 
carbohydrate  or  fat  has  nothing  to  do  with  the  intensity  of 
the  specific  dynamic  action.  Protein  retention  is  much  more 
readily  brought  about  on  a  mixed  diet  containing  large 
quantities  of  carbohydrates,  as  will  be  seen  in  a  subsequent 
chapter. 

Thus  far  in  this  book  the  influence  of  external  temper- 
ature upon  the  course  of  protein  metabolism  has  not  been 
discussed.  Rubner  has  shown  that  this  is  a  factor  of  profound 
significance.  It  has  already  been  demonstrated  how,  through 
chemical  regulation,  the  basal  requirement  of  the  body  is 
renexly  increased  by  increasing  cold  in  the  environment. 
Rubner2  compared  the  starving  metabolism  of  a  dog  at 
different  temperatures  with  that  of  the  same  dog  when  100, 
200,  and  320  grams  of  meat  were  ingested.  The  results  are 
presented  as  follows  in  terms  of  calories  produced  per  kilogram 
of  body  weight: 

1  Rubner:    "Die  Gesetze  des  Energieverbrauchs,"  1902,  p.  246. 

2  Rubner:   Ibid.,  p.  109. 


234 


SCIENCE    OF   NUTRITION 


INFLUENCE   OF   EXTERNAL   TEMPERATURE   ON   METABOLISM 
AFTER   PROTEIN   INGESTION 


Temperature. 


7 
IS 

20 

25 
30 


Starvation. 


86.4 
63.0 

55-9 
54-2 
56.2 


100  Gm.  Meat 

or  24  Cal. 

per  Kg. 


55-9 
55-5 
55-6 


200  Gm.  Meat 

or  48  Cal. 

per  Kc. 


77-7 

57-9 
64.9 

63-4 


320  Gm.  Meat 

or  81  Cal. 

per  Kg. 


87.9 
86.6 

76.3 
83.0 


One  hundred  grams  of  meat  did  not  change  the  metabolism 
at  200,  250,  or  300;  200  grams  of  meat  had  no  effect  at  200  or  at 
70,  but  at  2  50  and  at  300  there  was  an  increase,  although  the 
food  contained  fewer  calories  than  the  requirement.  With  320 
grams  of  meat  there  was  a  great  increase  above  the  starvation 
requirement,  except  at  70,  where  it  is  a  maintenance  diet  and 
the  metabolism  remains  unchanged.  In  other  words,  at  a 
temperature  of  300  the  specific  dynamic  action  of  this  amount 
of  protein  is  capable  of  increasing  the  heat  production  above 
that  of  starvation  by  about  53  per  cent.,  while  at  70  there  is  no 
change  whatever.  It  is  also  evident  that  at  a  high  temperature 
even  a  small  quantity  of  protein,  such  as  200  grams  of  meat, 
causes  a  considerable  rise  of  metabolism. 

Rubner  gives  the  metabolism  in  terms  of  calories  per 
kilogram  after  the  ingestion  of  550  grams  of  meat  or  173.8 
calories  per  kilogram  of  body  weight  in  a  dog,  as  follows: 

Temperature.  Starvation.    550  Grams  Meat.     Increase. 

4.20 128. 1  133-5  4.2  per  cent. 

14.5° 100. 9  no. 9  9.9        " 

22.1° 70.7  IOI.O  42.9  " 

30. 70 62.0  117. 2        S9.0       " 


In  certain  cases  after  food  ingestion  the  carbon  dioxid 
excretion  may  remain  constant  at  different  temperatures  of 
environment.  This  action  is  seen  in  the  dog  mentioned  on 
this  page  after  he  had  eaten  320  grams  of  meat  at  various  room 
temperatures.  The  increase  in  body  metabolism  due  to  the 
stimulus  of  cold  (chemical  regulation)  is  not  necessary,  since 


THE    INFLUENCE    OF   PROTEIN   FOOD 


235 


heat  in  excess  of  the  requirement  is  already  available.  All 
that  is  needed  is  the  arrangement  of  avenues  of  escape  for  the 
excess  of  heat  produced  from  the  food  ingested  (physical  regu- 
lation). This  physical  regulation  is  brought  about  by  the 
evaporation  of  water  and  by  a  change  in  the  distribution  of 
the  blood. 

How  the  increased  evaporation  of  water  enters  as  a  re- 
frigerating factor  is  beautifully  shown  in  the  experiment  on 
the  dog  (p.  234)  which  fasted  and  then  received  100,  200,  and 
320  grams  of  meat  at  various  room  temperatures.  The 
distribution  of  the  loss  of  heat  by  radiation  and  conduction 
and  by  the  evaporation  of  water  was  as  follows : 

DISTRIBUTION    OF    HEAT    LOSS    FROM    A    DOG    AFTER    MEAT 

INGESTION 


Hunger. 

100  Grams  Meat. 

200  Grams  Meat. 

320  Grams  Meat. 

Tem- 
pera- 
ture. 

Cal.  from 
Radia- 
tion and 
Conduc- 
tion. 

Cal.  from 
Evapora- 
tion of 
Water. 

Cal.  from 
Radia- 
tion and 
Conduc- 
tion. 

Cal.  from 
Evapora- 
tion of 
Water. 

Cal.  from 
Radia- 
tion and 
Conduc- 
tion. 

Cal.  from 
Evapora- 
tion of 
Water. 

Cal.  from 
Radia- 
tion and 
Conduc- 
tion. 

Cal.  from 
Evapora- 
tion of 
Water. 

7°... 

15°. •• 

20°. . . 

250... 
3°°... 

78.5 
55-3 
45-3 
41.0 

33-2 

7-9 

7-7 

10.6 

13.2 

23.0 

46.7 

34-i 

9.2 

21-5 

67.I 

46.7 
49-5 

27.8 

10.6 
II. 2 
15-4 

35-6 

78.5 
76.2 

34-5 

9-4 
10.4 

48.5 

It  is  evident  from  the  above  that  the  greater  part  of  the  loss 
of  heat  at  a  low  temperature  was  by  radiation  and  conduction, 
but  at  a  high  temperature  (300)  the  loss  by  the  evaporation  of 
water  was  largely  increased.  The  extra  heat  production  on 
account  of  the  specific  dynamic  action  of  the  protein  was  lost 
through  the  increased  evaporation  of  water.  Much  meat  on 
a  hot  day  would,  therefore,  seem  contraindicated. 

While  the  chemical  regulation  protects  the  body  from  an 
abnormal  fall  in  temperature,  the  physical  regulation  prevents 
an  abnormal  rise  in  temperature.  The  organism  may  be  at 
times  under  the  influence  of  one  means  of  regulation,  at  times 


236  SCIENCE   OF   NUTRITION 

of  the  other,  and  without  being  conscious  of  any  difference. 
Cold-blooded  animals  have  inadequate  chemical  regulation, 
and  their  temperature  falls  with  that  of  their  surroundings  (see 

P-  114). 

A  study  of  the  specific  dynamic  action  of  protein  in  its  re- 
lation to  temperature  changes  gave  Rubner1  new  points  of 
view.  He  saw  (experiment  on  p.  234)  that  by  chemical 
regulation  the  metabolism  in  a  fasting  dog  was  increased  from 
54  to  86  calories  per  kilogram,  an  increment  of  32.  And  he 
likewise  observed  that  after  the  ingestion  of  320  grams  of  meat 
the  heat  produced  at  a  room  temperature  of  300  rose  from  56 
in  starvation  to  83,  a  difference  of  27  calories.  The  source  of 
the  increase  through  chemical  regulation  is  known  to  be 
chiefly  in  the  muscles.  The  increase  brought  about  by  protein 
ingestion  had  been  shown  by  Rubner  to  be  due  not  to  any 
such  thing  as  intestinal  activity  (see  p.  231),  but  rather  to 
some  specific  heat-raising  effect  of  protein  metabolism  itself. 
It  was  apparent  that  these  two  sources  of  increased  heat 
might  enter  into  a  reciprocal  arrangement,  because  on  cooling 
the  atmosphere  in  which  the  dog  lived  to  70  C.  the  metab- 
olism, after  the  ingestion  of  320  grams  of  meat,  remained  at 
87.9  calories  in  contrast  with  83.0  on  feeding  at  300.  Here 
the  heat  due  to  the  specific  dynamic  action  was  used  in  replace- 
ment of  that  induced  by  chemical  regulation.  This  illustrates 
Rubner's  modified  idea  of  his  compensation  theory,  or  a  reci- 
procity between  heat  produced  in  the  muscles  by  chemical 
regulation  and  the  extra  heat  production  brought  about 
through  the  ingestion  of  food. 

Since  the  extra  heat  production  after  food  ingestion  could 
be  utilized  instead  of  heat  from  chemical  regulation,  Rubner 
perceived  that  the  true  increase  through  specific  dynamic 
action  could  be  measured  best  at  the  temperature  of  330, 
where  there  was  no  reflex  increase  in  metabolism  through 
chemical  regulation. 

It  was  especially  important  to  make  experiments  regarding 

1  Rubner:   "Energiegesetze,"  p.  145. 


THE    INFLUENCE    OF    PROTEIN    FOOD 


237 


the  action  of  food-stuffs  at  a  temperature  of  330,  for  that  is  the 
temperature  with  which  man  surrounds  his  skin.  By  means 
of  clothes  and  artificial  heating  man  constantly  tries  to  re- 
move himself  from  the  influence  of  chemical  regulation.  His 
daily  life  is  practically  under  the  influence  of  a  tropical  climate. 
His  metabolism  is  unchanged  from  the  normal  when  he  is 
immersed  in  a  bath  at  330.1 


0 

Mea 

t 

u 

•). 

hsss 

21 

S 

>T.Fat 

M 

at 

HD 

it 

.if. 

* 

/ 

Fat 

10U 
$07.? 

Mt 

ut 

Hunt 

er 

— 

-- 

__. 



-- 

H 

urge 

■ 

_ 

. 

Hun 

ger 

-i 

»L 

>_ 

*» 

in. 

* 

6 

ugar 

•* 
$ 

9  & 

•n   ^ 

s 

•a 

0   fc 

"  -a 

i 

' 

t          i 

I 

t 

L          1 

*      / 

£«j 

1 
1 

# 

r  t 

xjber 

in 

te 

if. 

Sm 

i 

* 

>  ■    j) 

) 

Fig.  16. — Rubner's  chart  indicating  the  specific  dynamic  action  of  different 
food-stuffs  ingested  at  a  room  temperature  of  33  °.  The  dotted  line  indicates 
the  height  of  the  fasting  metabolism. 


Rubner,  therefore,  planned  an  experiment  in  which  a  dog 
was  kept  at  a  temperature  of  33°.  At  times  the  animal  was 
made  to  fast  in  order  that  the  basal  requirement  could  be  de- 
termined, and  during  other  definite  periods  meat,  fat,  and  car- 
bohydrates, either  alone  or  combined,  were  ingested,  and  the 
increased  metabolism  due  to  the  varying  dietaries  was  noticed. 
The  experiment  extended  over  a  period  of  forty-six  days. 

1  Rubner:   "Archiv  fur  Hygiene,"  1903,  xlvi,  390. 


238  SCIENCE   OF   NUTRITION 

A  summary  of  the  results  obtained  is  graphically  illustrated 
by  the  accompanying  Fig.  16,  which  has  been  taken  from 
Rubner.1 

'It  is  clearly  evident  that  meat  ingestion  raises  the  metab- 
olism most,  fat  next,  and  sugar  least  of  all  the  food-stuffs.  The 
ingestion  of  the  starvation  requirement  for  energy  in  the  form 
of  fat  raises  the  metabolism  12.7  per  cent.;  in  the  form  of 
sugar,  5.8  per  cent.  During  the  two  periods,  when  approxi- 
mately 100  per  cent,  of  the  basal  requirement  was  ingested  as 
meat,  there  was  an  average  increase  in  the  metabolism  of  36.7 
per  cent. 

After  making  deductions  for  the  effect  of  the  fat  contained 
in  the  meat  given,  Rubner  computed  that  there  was  an  average 
increase  in  metabolism  of  30.94  calories  for  100  calories 
contained  in  the  protein  of  the  diet  in  the  resting  animal  when 
it  was  outside  of  the  influence  of  the  chemical  regulation  of 
temperature.  The  action  of  gelatin  is  similar,  the  increase 
in  metabolism  being  28  per  cent,  for  every  100  calories  in  the 
gelatin  ingested. 

Again  Rubner2  has  determined  the  amount  of  the  metab- 
olism of  a  fasting  dog  and  that  of  the  same  dog  made  diabetic 
with  phlorhizin  (see  p.  474).  Under  the  latter  circumstances 
the  protein  metabolism  is  greatly  increased.  He  found  that 
for  every  100  calories  increase  in  body  protein  broken  down 
there  was  an  increased  heat  production  of  31.9  calories.  Here 
was  a  rise  in  heat  production  not  due  to  protein  ingestion  and, 
therefore,  not  due  to  intestinal  work,  but  due  to  the  mere  fact 
of  increased  protein  metabolism  in  starvation.  The  specific 
dynamic  action  of  protein  then  may  thus  be  tabulated: 

INCREASED    HEAT    PRODUCTION    FOR    EVERY    100    CALORIES 
INGESTED   OR   METABOLIZED 

Meat  protein 30.9 

Gelatin ". 28.0 

Body  protein  (phlorhizin  diabetes) 31.9 

The  dog  of  Williams,  Riche,  and  Lusk  showed  an  in- 
crease   of    30    calories    in    heat    production    for   every    100 

'Rubner:  "Energiegesetze,"  p.  322.  2  Rubner:  Ibid.,  p.  370. 


THE   INFLUENCE    OF   PROTEIN   FOOD  239 

calories  contained  in  the  protein  of  the  1200  grams  of  meat 
ingested. 

It  has  furthermore  been  shown  by  Falta,  Grote,  and  Stae- 
helin1  that  casein  and  the  ammo-acids  resulting  from  the 
hydrolysis  of  casein  when  given  to  a  dog  exert  the  same 
specific  dynamic  action  as  do  the  proteins  of  meat. 

That  these  results  are  not  limited  in  their  application  is 
shown  by  Rubner's2  experiment  on  a  man  who  was  given  120 
per  cent,  of  the  starvation  requirement  of  energy  first  in  the 
form  of  sugar  and  then  of  meat.  The  metabolism  was  as 
follows : 

Starvation 2042  calories  in  24  hours. 

Sugar  alone 2087 

Meat  alone 2566       " 

As  neither  man  nor  dog  ever  lives  on  meat  alone  except  under 
forced  feeding,  the  results  are  not  usually  so  pronounced  as  in 
the  above  case. 

Average  mixed  diets,  according  to  Rubner,  must  contain 
between  11  and  14  per  cent,  more  than  the  calories  produced  in 
fasting  in  order  to  constitute  an  ingestion  minimum  for  the 
maintenance  of  a  man  in  caloric  equilibrium. 

One  must  now  pass  to  the  discussion  of  the  cause  of  the 
specific  dynamic  action  of  protein. 

In  1 88 1  Voit  laid  down  the  principle  that  the  intensity 
of  metabolism  in  the  cells  was  modified  by  the  quality  and 
quantity  of  the  food  materials  brought  to  them  by  the  blood. 
He  believed  that  the  inherent  power  of  the  cells  to  metabolize 
was  augmented  by  the  presence  of  increased  quantities  of 
food-stuffs.  Rubner  developed  another  conception.  He  de- 
clared that  the  fundamental  metabolism  of  a  normal  warm- 
blooded animal  was  always  constant,  and  that  the  effect  of 
food  ingestion  did  not  change  this.  The  increased  heat 
production  which  followed  the  taking  of  food  was  due  to  heat 
developed  from  a  lot  of  intermediary  reactions  and  oxidations, 

1  Falta,  Grote,  and  Staehelin:    "Hofmeister's  Beitrage,"  1907,  ix,  334. 

2  Rubner:   "Energiegesetze,"  p.  410. 


240  SCIENCE   OF   NUTRITION 

and  had  nothing  whatever  to  do  with  the  fundamental  level 
of  the  cellular  requirement  of  energy  which  was  entirely- 
unchanged.  Thus,  when  protein  was  metabolized  it  could 
supply  energy  for  the  maintenance  of  true  cellular  activity 
in  so  far  as  glucose  was  produced  from  it,  whereas  other 
intermediary  cleavage  products  were  simply  oxidized  with  the 
production  of  extra  heat,  which  was  in  no  way  involved  in  the 
life  processes  of  the  cells.  The  utilization  of  energy  in  protein 
might  be  compared  with  the  burning  of  a  tree  as  fuel  for  the 
steam  engine,  the  trunk  of  the  tree  being  used  as  fuel  within 
the  engine  for  the  production  of  power,  whereas  the  limbs  and 
twigs  are  burned  as  brush  outside  and  supply  only  heat. 
The  theory  may  be  schematically  indicated  as  follows: 

STARVATION  REQUIREMENT  OF  POTENTIAL  ENERGY  BY  CELLS 

=    100   CALORIES 
140  Calories  in  Protein  of  Meat  Ingested 


40  Calories  =   free  heat  liberated  in       100    Calories     =     Potential    energy 
early  cleavage,  available  in  replace-  from    protein     available    for    cell 

ment  of  heat  of  chemical  regulation.  life. 

This  conception  was  founded  on  the  erroneous  idea  that 
sugar  exerted  little  or  no  specific  dynamic  action  (see  p.  294). 

Experiments  were  instituted  in  the  author's  laboratory1 
with  the  intention  of  more  fully  establishing  the  truth  of 
Rubner's  theories  of  specific  dynamic  action.2  It  was  known 
that  glycocoll  and  alanin  were  completely  convertible  into 
glucose  in  the  diabetic  organism,  whereas  glutamic  acid  was 
in  part  so  converted,  three  of  its  five  carbon  atoms  passing  into 
glucose,  the  other  two  being  oxidized.  It  follows  from 
Rubner's  hypothesis  that  glycocoll  and  alanin  should  exert 
no  specific  dynamic  action,  whereas  glutamic  acid  should 
manifest  this  phenomenon.  The  reverse  proved  to  be  true: 
glycocoll  and  alanin  are  capable  of  greatly  increasing  the 
heat  production,  whereas  the  strong  dibasic  glutamic  acid  is 
without  influence.     Glycocoll  and  alanin  produce  powerful 

JLusk:  "Journal  of  Biological  Chemistry,"  1012-13,  xiii,  155. 
2  The  argument  here  presented  is  to  be  found  in  Lusk:    "Journal  of  Bio- 
logical Chemistry,"  1915,  xx,  p.  viii. 


THE    INFLUENCE    OF   PROTEIN   FOOD 


241 


effects,  lasting  eight  and 
five  hours  respectively, 
whereas  on  giving  those 
quantities  of  glucose  into 
which  the  amino-acids  are 
convertible  only  an  al- 
most negligible  influence 
is  observable. 

These  facts  are 
brought  out  in  Fig.  17. 
It  should  be  remembered 
that  25  grams  of  glycocoll 
and  20  grams  of  alanin 
are  each  convertible  into 
20  grams  of  glucose. 
Leucin  and  tyrosin  ex- 
erted only  a  slight  effect 
upon  the  heat  production. 
A  mixture  of  5.5  grams 
each  of  glycocoll,  alanin, 
glutamic  acid,  and  tyro- 
sin, containing  3.46  grams 
of  nitrogen,  produced 
about  the  same  specific 
dynamic  action  as  100 
grams  of  meat  which  con- 
tain about  3  grams  of 
nitrogen. 

The  curve  of  nitrogen 
elimination  shown  in  Fig. 
17  does  not  truly  repre- 
sent the  rapidity  of  the 
metabolism  of  the  amino- 
acids.  If  instead  of  using 
the  hourly  extra  nitrogen 
eHmination  after  giving 
16 


m 


E.K 


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3    & 

o 

£.3 

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da. 


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5.2. 
S-"  <" 

1-1  -:. 
o  3 
en  aq 


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)6.        20  6.         20  G.         206.    5.5  G.or  each  1 
jin  Glutamic  acid  Leucin     Tyrosine  of  the 5  amino  l\ 

acids  3.46  G.N 

'  3 

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HCD 

242 


SCIENCE    OF   NUTRITION 


glycocoll  or  alanin  one  employs  the  "extra  glucose"  elimina- 
tion after  giving  these  substances  to  a  dog  with  phlorhizin 
glycosuria,  it  is  discovered  that  the  maximum  breakdown 
of  the  amino-acid  takes  place  during  the  second  hour  after 
their  ingestion.  The  following  chart  (Fig.  18)  shows  such 
experiments  as  accomplished  by  Csonka  :x 


K 

^f.p          /  \                         i 

rrMT|                      /         V              -             \-            Jl- 

LtN  1                     f-       \ 

1~-  -V                                    "  ----  -  "- 

pir_        _z          _£ _I                          —      X 

w           t           i 

it            *                X                     T 

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2   jiI^Jl.          II 

?n--lt£-,£—  I-5SII     __     I- _lt -- 

CV _^H                     «,_._        -+- 

3LS                      As*    *-      X4I                                  It 

zr£             -Ss»     it        nt 

ittn                                    ^* 

\K  ...  ..dj     *    ,,.     .  .                      v.  »  \ 

15      Ig    *—          ~                   S*^                                        _ 

1-3                    ^  2Pi 

jtj               ____     *     £33,- 

4V       it        IT                  '  %£ 

,o  _33 _      _    X-2W_ _ 

10  //                         i  \- 

it           i                ->t-i^* 

C                                                                                                                           -SiA             ^> 

II                                                                   *i        \ 

r  Ji                                                                      5^- ^Sl_5^_ 

5  It            It                                   -   -   k      \          ^11 

11        J~                                               N"\ I 

/;                                                       ^^*        \ 

I'                                                                                              V              v 

„ i:              ±iiii:_                      N,     js 

HOURS  -  CAT 

J  Z  3         4  5  6  7         8 

GLUCOSE  FROM   16  glUINGESTED    GLUCOSE 

GLUCOSE  FROM  £O0miNGESTED    GLYCOCOLL 

GLUCOSE  FROM   20gTlYlNGESTED    ALANINE 

Fig.  1 8. 

This  chart  shows  that  the  rapidity  of  the  absorption  and 
elimination  of  glucose  ingested  in  phlorhizin  glycosuria  is 
almost  the  same  as  the  rapidity  of  the  absorption,  deamination, 
synthetic  sugar  production,  and  the  elimination  of  such  sugar 
after  the  administration  of  an  iso-glucogenic  quantity  of 
glycocoll  and  a  comparable  quantity  of  alanin. 

1  Csonka:   "Journal  of  Biological  Chemistry,"  1915,  xx,  539. 


THE   INFLUENCE    OF   PROTEIN   FOOD  243 

It  may  be  added  that  Janney1  reports  that  after  giving 
meat  to  a  phlorhizinized  dog  the  extra  sugar  appears  in  the 
urine  quite  as  rapidly  as  after  giving  glycocoll  or  alanin. 
The  rapidity  of  the  attack  of  digestive  enzymes  upon  protein 
must,  therefore,  be  much  greater  than  has  hitherto  been  sup- 
posed. 

Using  the  results  obtained  with  glycocoll  and  alanin,  Lusk2 
found  that  the  hours  of  the  greatest  heat  production  after 
the  administration  of  these  substances  were  coincident  with 
the  hours  of  their  greatest  metabolism.  Also,  it  was  found 
that  the  increase  in  metabolism  after  giving  glycocoll  and 
alanin  together  is  equal  to  the  sum  of  the  effects  produced  by 
either  alone.  Furthermore,  the  increase  of  metabolism  after 
giving  20  grams  of  glycocoll  is  twice  as  great  as  after  giving  10 
grams.  Similar  relations  obtain  after  different  quantities  of 
alanin.  This  accords  with  Rubner's  discovery  that  the  in- 
tensity of  the  specific  dynamic  action  is  proportional  to  the 
quantity  of  protein  ingested.  When  one  compares  the  heat- 
increasing  power  of  glycocoll  and  alanin  upon  metabolism,  it 
is  found  that  this  power  isnot  proportional  to  their  respective 
abilities  to  form  sugar,  but  rather  to  the  number  of  molecules 
of  glycollic  and  lactic  acids  which  they  are  respectively  sup- 
posed to  yield  on  deamination. 

It  was  found  in  one  experiment  that  the  entire  energy 
content  of  the  ingested  glycocoll  reappeared  in  the  extra 
output  of  energy  given  off  by  the  dog  in  the  form  of  heat. 
The  course  of  inquiry  into  this  phenomenon  which  naturally 
suggests  itself  is  whether  glycocoll  is  without  action  upon  the 
body-cells;  that  is,  whether  it  merely  explodes  and  yields  heat, 
or  whether  it  directly  stimulates  the  cells,  thereby  raising 
metabolism  to  a  higher  level.  This  point  was  determined  by 
giving  glycocoll  to  a  phlorhizinized  animal.  Under  these 
circumstances  there  is  no  oxidation  of  the  material  ingested 
and  the  energy  content  of  the  glycocoll  is  eliminated  in  the 

1  Janney:   "Journal  of  Biological  Chemistry,"  1915,  xxii,  191. 

2  Lusk:   Ibid.,  1915,  xx,  555. 


244 


SCIENCE   OF   NUTRITION 


urine  in  the  form  of  sugar  and  urea.  The  metabolism  was 
largely  increased,  notwithstanding  the  fact  that  there  was  no 
oxidation  of  the  ingested  material.  Exactly  the  same  phe- 
nomenon followed  the  ingestion  of  alanin  in  phlorhizin  gly- 
cosuria. The  ingestion  of  glucose  was  without  effect  even  after 
70  grams  had  been  given.  The  cause  of  the  specific  dynamic 
action  of  glycocoll  and  alanin  therefore  lies  in  a  chemical 
stimulation  of  the  cells,  causing  them  to  metabolize  more 
material.  This  confirms  the  older  view  of  Voit  that  the  action 
of  food  increases  the  power  of  the  cells  to  metabolize. 

An  experiment1  which  shows  the  effect  of  giving  20  grams 
of  glycocoll  to  a  phlorhizinized  dog  is  here  reproduced : 

DOG  III,  MARCH  25,  1915,  EXPERIMENT  104.  BASAL  PHLORHIZIN 
METABOLISM  AS  AFFECTED  BY  20  GRAMS  OF  GLYCOCOLL  IN 
210  C.C.  OF  WATER  AT  38°  PLUS  1  GRAM  OF  LIEBIG'S  EXTRACT 


Hours. 

R.  Q. 

Calories. 

Indirect. 

Direct. 

1 

Basal 

o.733 
0.716 

23-78 
23.82 

24-53 
23.84 

Average 

Glycocoll,  20  grams 

Average 

3 
4 
5 
6 

7 

0.724 

0.707 

0-745 
0.700 
0.702 

23.80 

34-21 
3I-65 
29.24 

25-99 

24.18 

32-34 
29.47 
30.07 
26.85 

0.720 

30.27 

29.68 

Although  glycocoll  was  not  oxidized,  but  appeared  as 
glucose  and  urea  in  the  urine,  yet  there  was  a  considerable 
increase  in  the  heat  production  after  its  ingestion  in  phlorhizin 
glycosuria.  It  is,  therefore,  evident  that  the  cause  of  the 
specific  dynamic  action  of  glycocoll  is  independent  of  the 
oxidation  of  glycocoll  or  the  liberation  of  its  energy  content. 
These  results,  which  were  first  presented  at  the  International 

1  Lusk:   hoc.  cit.,  p.  612. 


THE   INFLUENCE    OF   PROTEIN   FOOD 


245 


Physiological  Congress  held  in  Groningen  in  1913,1  have  been 
fully  confirmed  by  Grafe,2  who  reports  that  after  giving  50 
grams  of  glycocoll  to  a  normal  dog  the  oxygen  absorption 
rose  77  per  cent.,  while  in  man  the  increase  was  14  per  cent. 

The  chemical  stimulus  to  the  cells  does  not  reside  in  the 
amino-acids  themselves,  for  there  is  no  accumulation  of 
amino-acids  in  the  tissues  after  the  ingestion  of  meat  in  large 
quantities.  (See  Van  Slyke,  Wishart,  p.  80.)  Also  when 
protein  is  deposited  in  the  form  of  new  tissues  these  amino- 
acids  exert  no  specific  dynamic  influence.  Rubner3  gives  the 
following  example  of  the  stage  of  the  deposit  of  protein  with- 
out a  rise  in  the  metabolism  of  a  dog: 


Starvation. 
Meat 


to  Body. 

Calories  per  Kg 

+  8.7 

43.26 
44.48 

The  researches  of  Hoobler4  have  shown  the  same  to  be  true 
of  the  baby,  as  appears  from  the  following  data: 


Protein 
Ingested.- 

Protein 
Destroyed. 

Protein 
Added  to  Body. 

Calories  or 
Metabolism. 

High  protein  diet. .  . 
High  protein  diet. .  . 

Grams. 
33-1 
43-3 

Grams. 
18.0 
18.9 

Grams. 
24.4 

363 
363 

Such  facts  demonstrate  that  the  mere  absorption  of  amino- 
acids  and  their  rebuilding  into  new  protoplasm  does  not 
increase  the  metabolism. 

Since  the  hours  of  the  highest  heat  production  after  giving 
glycocoll  and  alanin  are  the  hours  of  the  maximal  metabolism 
of  these  amino-acids,  it  is  obvious  that  the  metabolism  prod- 
ucts, such  as  glycollic  or  lactic  acids  (see  pp.  190-194),  are 
indicated  as  the  probable  chemical  stimuli  which  act  upon  the 

1  Lusk:   ''Archives  of  Internal  Medicine,"  1913,  xii,  485. 

2  Grafe:   "Deutsches  Archiv  fur  klin.  Med.,"  1915,  cxviii,  1. 

3  Rubner:   "Gesetze  des  Energieverbrauchs,"  1902,  p.  256. 

4  Hoobler:   "American  Journal  of  Diseases  of  Children,"  1915,  x,  153. 


246  SCIENCE   OF   NUTRITION 

protoplasm  of  the  cells,  causing  them  to  oxidize  materials  in 
increased  measure. 

One  recalls  in  this  connection  the  permanently  increased 
metabolism  in  phosphorus-poisoning,  in  severe  anemias,  and  in 
persons  living  at  high  altitudes,  under  all  of  which  conditions 
lactic  acid  is  found  in  increased  amounts  in  the  blood  and  often 
in  the  urine.     (See  Chapter  XV.) 

That  the  chemical  stimulus  acts  on  protoplasm  directly  and 
not  through  excitation  of  the  nervous  system  is  to  be  inferred 
from  the  experiments  of  Tangl,1  who  noticed  an  increase  in  the 
heat  production  of  curarized  dogs  after  giving  tnem  protein. 

External  cold  acts  reflexly  through  the  nervous  system 
to  increase  metabolism  in  a  fasting  animal  and  thus  prevents 
a  fall  in  body  temperature  through  the  "chemical  regulation" 
of  body  temperature.  According  to  Rubner's  hypothesis,  the 
"free  heat"  liberated  in  the  intermediary  metabolism  of 
protein  can  be  used  in  lieu  of  that  derived  from  the  increased 
metabolism  induced  through  the  effect  of  cold.  In  the  light 
of  the  newer  researches,  however,  the  extra  heat  necessary 
to  preserve  the  body  from  a  fall  in  temperature  may  be 
derived  from  an  increased  metabolism  of  the  cell  itself, 
whether  this  be  induced  by  nerve  action  or  by  direct  chemical 
stimulation. 

It  may  be  that  the  mass  action  of  the  various  fragments 
produced  in  the  breakdown  of  protein  in  metabolism  is  also  a 
contributory  factor  in  the  higher  production  of  heat,  but  that 
it  is  the  main  factor  is  negatived  by  contrasting  the  different 
effect  of  20  grams  of  glutamic  acid  with  that  of  20  grams  of 
glycocoll,.the  effect  of  the  first  being  nil  and  that  of  the  latter 
powerful. 

The  influence  of  meat  ingestion  in  man  is  given  in  the 
following  table: 

1  Tangl:   "Biochemische  Zeitschrift,"  191 1,  xxxiv,  1. 


THE  INFLUENCE  OF  PROTEIN  FOOD 


247 


TABLE  SHOWING  THE  PERCENTAGE  INCREASE  IN  METABOLISM 
EACH  HOUR  AFTER  THE  INGESTION  OF  MEAT  BY  MAN 


N  tn 
Meat. 

Increase  in  Metabolism  in  Per  Cent. 

1 

2 

3 

4 

5 

6 

7 

8 

10      11 

Magnus-Lew1 

Grams. 
12 
IO.5 

23.9* 

8      6 

8 

32 
16 

15 

24 
12 
16 

34 
IS 
28 

26 

7 

27 

18 

26 

Gephart  and  Du  Bois2 

Gephart  and  Du  Bois2 

*  Chopped  meat  725  grams  +  100  grams  fat. 


In  the  last-named  experiment  protein  furnished  between 
25  and  40  per  cent,  of  the  total  calories  of  metabolism  in- 
stead of  the  average  normal  of  15  per  cent.  When  Grafe3 
administered  80  grams  of  alanin  or  50  grams  of  glycocoll 
to  a  man  the  specific  dynamic  action  caused  an  increase  in 
the  oxygen  absorption  of  7  and  14  per  cent,  respectively. 
The  specific  dynamic  action  of  protein  is  not  usually  as  great 
in  man  as  in  the  dog.  Du  Bois4,  however,  has  seen  a  rise  of  55 
per  cent,  in  the  metabolism  of  an  achondroplastic  dwarf  after 
giving  him  750  grams  of  meat. 

1  Magnus-Levy:    "Pfliiger's  Archiv,"  1894,  lv,  87. 

2  Gephart  and  Du  Bois:  "Archives  of  Internal  Medicine,"  1915,  xv,  835. 

3  Grafe:  Loc.  cit. 

4  Unpublished. 


CHAPTER  VIII 

THE  INFLUENCE  OF  THE  INGESTION  OF  FAT 

In  a  previous  chapter  it  was  shown  that  the  amount  of  fat 
in  the  fasting  organism  materially  affected  the  amount  of 
protein  burned.  Where  there  was  much  fat  present  little 
protein  was  consumed;  where  there  was  little  fat,  much  pro- 
tein burned;  and  where  there  was  no  fat,  protein  alone  yielded 
the  energy  necessary  for  life. 

The  ingestion  of  fat  alone  will  not  prevent  the  death  of  the 
organism  because  there  is  a  continual  loss  of  tissue  protein  from 
the  body,  which  finally  weakens  some  vital  organ  to  such  an 
extent  that  death  takes  place. 

In  a  fasting  animal  which  still  contained  fat,  Voit1  found 
that  the  ingestion  of  ioo,  200,  and  300  grams  of  fat  scarcely 
influenced  the  protein  metabolism.  The  latter  was  slightly 
increased,  if  anything.     Voit's  table  is  as  follows: 

Fat.                 Urea.  Fat.                 Urea. 

o 11. 9     300 12.0 

o 12.0       o 11. 9 

100 12.0       c 11.3 

200 12.4 

These  results  have  been  confirmed  by  Bartmann,2  who 
noted  that  fat  given  to  the  extent  of  150  per  cent,  of  the  energy 
requirement  was  readily  absorbed  and  spared  protein  to  a 
maximum  of  7  per  cent.  Sometimes  when  much  fat  was  given 
there  was  an  increased  elimination  of  nitrogen  in  the  urine,  at 
which  time  there  was  also  an  increased  amount  of  nitrogen  in 
the  stools. 

1  Voit:    "Physiologie  des  Stoffwechsels  und  der  Ernahrung,"  1881,  p.  128. 

2  Bartmann:    "Zeitschrift  fur  Biologie,"  1912,  lviii,  375. 

248 


THE  INFLUENCE  OF  THE  INGESTION  OF  FAT      249 

To  another  dog,  which  in  starvation  burned  96  grams  of 
fat,  Voit  gave  100  grams,  with  the  result  that  it  then  burned  97 
grams.  The  conditions  of  the  metabolism  in  these  cases  were 
therefore  identical.  The  fat  ingested  simply  burned  instead  of 
the  body's  fat,  but  the  total  amount  of  protein  and  fat  burned 
remained  the  same. 

One  reason  why  the  ingestion  of  fat  up  to  the  requirement 
does  not  alter  the  metabolism  may  be  found  in  the  observation 
of  Schulz1  that  in  starvation  there  is  an  increase  in  the  quantity 
of  fat  in  the  blood,  and  of  Rosenfeld2  that  the  amount  of  fat  in 
the  liver  increases.  He  finds  that  a  fasting  liver  contains  10 
per  cent,  of  fat.  If  carbohydrates  or  protein  (which  yields  car- 
bohydrate in  metabolism)  be  ingested,  the  fat  content  falls  to 
6.2  per  cent.  If  fat  be  given  to  a  fasting  dog,  the  liver  may 
contain  25  per  cent,  of  fat;  but  if  carbohydrates  are  ingested  at 
the  same  time,  the  liver  does  not  retain  the  fat,  which  must  be 
deposited  elsewhere.  Thus,  in  the  liver  there  is  an  antagonism 
between  glycogen  deposit,  which  follows  carbohydrate  inges- 
tion, and  fat  deposition. 

Pfliiger3  gave  a  dog  fat  alone  in  large  quantities  for  thirty 
days  and  found  that  the  fresh  substance  of  the  liver  at  the  end 
of  the  period  contained  45  per  cent,  of  fat  and  no  glycogen. 

Miescher  found  fat  globules  in  the  muscle-cells  of  salmon 
after  their  five  to  fifteen  months'  fast  in  fresh  water,  during 
which  time  they  had  laid  their  eggs.  It  is  undoubted  that  the 
deposits  of  fat  in  the  adipose  tissue  of  these  fishes  are  drawn  on 
in  starvation,  and  that  the  blood  then  carries  to  the  hungry  cells 
all  the  fat  they  require  for  their  continued  function.  Greene4 
states  that  large  quantities  of  fat  are  present  in  the  fibers  of  the 
great  lateral  muscle  of  the  Columbia  River  salmon  at  the 
beginning  of  its  travels  up  the  river,  and  this  fat  remains 
there  in  strikingly  uniform  quantity  during  the  whole  of  the 
migration  journey.     It  seems  that  the  fat  supply  to  the  cells 

1  Schulz:   "Pfltiger's  Archiv,"  1896,  lxv,  299. 

2  Rosenfeld:    "Ergebnisse  der  Physiologie,"  1903,  ii,  I,  86. 

3  Pfliiger:   "Pfliiger's  Archiv,"  1907,  cxix,  123. 

4  Greene:   "Journal  of  Biological  Chemistry,"  191 2,  xi,  p.  xviii. 


250  SCIENCE    OF    NUTRITION 

is  regulated  by  the  quantity  of  other  foods  available,  and  that 
even  in  starvation  there  is  at  first  ample  fat  to  meet  the 
requirement  of  the  organism  (see  p.  100).  These  are  impor- 
tant principles  which  will  be  further  discussed  when  the 
subject  of  fatty  infiltration  is  considered.  (See  chapter  on 
Diabetes.) 

The  method  of  the  oxidation  of  fat  has  already  been 
described  (see  p.  182),  and  one  would  expect  to  find  /3-oxy- 
butyric  acid  as  an  end-product  of  this  metabolism.  In  fact, 
the  blood  of  normal  human  subjects,  as  well  as  the  blood  of 
dogs,  pigs,  and  cattle,  contains  usually  a  little  less  than  1.5 
mg.  of  /3-oxybutyric  acid  in  100  c.c.1  Sassa2  reports  between 
1  and  2  mg.  to  be  widely  distributed  in  the  blood  and  organs  of 
man  and  various  mammals.  In  normal  conditions  this  end- 
product  is,  therefore,  present  in  only  minimal  amounts. 

When  fat  is  oxidized  in  excess,  as  in  fasting,  /3-oxybutyric 
acid  appears  in  the  urine  (see  p.  182).  So  also  when  fat  forms 
the  main  portion  of  the  diet  the  same  phenomenon  occurs. 
Forssner3  gave  a  man  a  diet  which  contained  3380  calories,  of 
which  only  160  were  in  carbohydrate.  The  last  meal  was 
taken  at  4.00  p.  m.,  and  then  olive  oil  was  given  at  9.00  p.  m. 
The  urines  between  11.00  p.  m.  and  10.00  a.  m.  contained  the 
following  amounts  of  acetone  bodies : 

Total  Acetone  Bodies,     /3-Oxybutyric  Acid, 
Grams.  Grams. 

No  olive  oil 5.1 1  3.69 

40  grams  olive  oil 9.16  7.22 

60  grams  olive  oil 9.96  8.08 

80  grams  olive  oil 11.80  9.52 

These  results  indicate  the  formation  of  /3-oxybutyric  acid 
in  large  amounts. 

The  work  of  Bloor4  has  shown  that  after  giving  fat  to  a 
dog  there  is  a  gradual  rise  in  the  fat  content  of  the  blood,  the 

1  Marriott:    "Journal  of  Biological  Chemistry,"  1914,  xviii,  507. 

2  Sassa:    "Biochemische  Zeitschrift,"  1914,  lix,  362. 

3  Forssner:   "Skan.  Archiv  fur  Physiologie,"  1910,  xxiii,  305. 

4  Bloor:   "Journal  of  Biological  Chemistry,"  1914,  xix,  1. 


THE    INFLUENCE    OF    THE   INGESTION   OF   FAT  25 1 

maximum  being  attained  in  the  sixth  hour,  after  which  there  is 
a  fall.     The  following  shows  an  example : 

Blood-fat 
Per  Cent. 

24  hours  after  food 0.6 

3I  hours  after  100  ex.  olive  oil 0.73 

6j  hours  after  100  c.c.  olive  oil 1.20 

8    hours  after  100  c.c.  olive  oil 0.87 

Furthermore,  when  fat  was  injected  intravenously  in 
such  quantity  that  the  fat  content  of  the  blood  was  doubled, 
the  excess  disappeared  within  five  minutes  after  the  cessation 
of  the  injection. 

Work  of  fundamental  character  by  Magnus-Levy1  showed 
the  influence  of  the  ingestion  of  very  fat  bacon  upon  the  metab- 
olism of  the  dog.  Respiration  experiments  lasting  about 
thirty  minutes  each,  using  the  Zuntz  method,  were  made  upon 
a  dog  breathing  through  a  tracheal  cannula.  These  showed 
that  after  giving  140  grams  of  fat  bacon  the  metabolism  in- 
creased from  the  end  of  the  third  hour  through  the  eighth 
to  a  height  which  was  about  10  per  cent,  above  the  orig- 
inal basal  level  as  measured  twenty-four  hours  after  the  last 
ingestion  of  food.  After  320  grams  of  fat  bacon  had  been 
taken  the  metabolism  showed  a  maximal  increase  of  19  per 
cent,  from  the  end  of  the  third  hour  through  the  sixth. 
The  increased  metabolism  extended  from  the  fourth  to 
the  thirteenth  hours  after  food  ingestion,  and  then  subsided 
to  the  original  basal  level.  The  total  increase  in  heat  pro- 
duction could  be  estimated  as  2.5  per  cent,  of  the  energy 
content  of  the  fat  ingested.  The  environmental  temperature 
of  the  dog  varied  between  160  and  190,  and  all  extraneous 
movements  were  avoided. 

In  man,  after  the  administration  of  210  grams  of  butter, 
Magnus-Levy  noted  a  maximal  increase  of  9  to  14  per  cent, 
above  the  basal  metabolism  during  the  seventh  hour.  During 
the  eighth  hour  the  increase  was  only  6  to  8  per  cent,  above 
the  basal  metabolism. 

1  Magnus-Levy,  A.:   "Arch.  f.  d.  ges.  Physiol.,"  1894,  lv,  1. 


252  SCIENCE   OF   NUTRITION 

The  influence  of  external  temperature  on  the  heat  pro- 
duction after  ingesting  fat  above  the  requirement  is  similar  to 
that  after  meat  ingestion,  only  not  so  pronounced.  Rubner1 
gives  the  following  table,  showing  the  effect  of  the  ingestion  of 
1 7 1.3  calories  in  fat  per  kilogram  of  dog: 

SPECIFIC  DYNAMIC  ACTION  OF  FAT 

1 7 1.3  calories  in  fat  per  kg.  dog  were  ingested. 
Calories  per  Kilo. 
Temperature.  Starvation.         After  Fat  Ingestion.  Increase. 

2. 70 152. 1  155-5  +  2.2  per  cent. 

15-5° 83.1  93.4  +12.4       " 

3i-°° 64.5  79.9  +23.9       " 

At  2. 70  the  excess  ingested  above  the  requirement  amounted 
to  12.6  per  cent.,  and  the  increase  in  heat  production  was  2.2 
per  cent.  At  310  the  excess  of  food  calories  above  the  re- 
quirement was  165  per  cent.,  and  the  increase  in  heat  produc- 
tion was  23.9  per  cent.  In  this  instance  100  per  cent,  of  the 
requirement  may  be  calculated  to  raise  the  metabolism  14.4 
per  cent,  at  a  temperature  of  310.  This  represents  the  specific 
dynamic  effect  of  fat  on  the  metabolism. 

Murlin  and  Lusk2  were  not  able  to  find  so  great  a  specific 
dynamic  action  in  the  dog  as  Rubner  found.  They  gave  to  a 
dog  an  emulsion  containing  75  grams  of  fat  with  692  calories 
of  energy,  or  145  per  cent,  of  the  basal  energy  requirement  of 
the  animal.  The  total  increase  of  heat  production  was  28.8 
calories  or  4.1  per  cent,  of  the  energy  in  the  fat.  The  experi- 
ments were  carried  out  at  an  environmental  temperature  of 
260  to  2 70  in  a  respiration  calorimeter,  and  the  results  are 
plotted  in  the  form  of  a  chart,  as  shown  on  p.  253.  (For  the 
effect  of  glucose  and  fat  see  also  p.  300.) 

The  experiment  shows  that  after  the  ingestion  of  fat  the 
heat  production  gradually  rises  till  the  sixth  hour  to  a  maxi- 
mum 30  per  cent,  above  the  basal  metabolism,  and  then  falls 
slowly  to  the  basal  level,  which  is  reached  ten  hours  after  the 

1  Rubner:   "Energiegesetze,"  1902,  p.  119. 

2  Murlin  and  Lusk:    "Journal  of  Biological  Chemistry,"  1915,  xxii,  15. 


THE  INFLUENCE  OF  THE  INGESTION  OF  FAT     253 

fat  has  been  taken  (Fig.  19).     This  curve  of  increasing  me- 
tabolism accords  with  the  curve  of  increasing  fat  content  in 


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Fig.  19.— The  effect  of  fat  and  of  glucose  plus  fat  upon  the  heat  production. 

the  blood  as  shown  by  Bloor,  and  indicates  that  the  heat 
production  may  be  increased  by  increasing  the  number  of 
metabolites  available  for  cell  nutrition. 


254  SCIENCE   OF   NUTRITION 

It  appears  from  the  respiratory  quotients  that  the  increase 
in  heat  production  is  entirely  at  the  expense  of  ingested 
fat.  The  respiratory  quotients  as  determined  for  the  basal 
metabolism  averaged  0.84,  and  after  fat  ingestion  0.79. 
Calculation  showed  that  the  amounts  of  protein  and  glycogen 
oxidized  during  the  two  series  of  experiments  were  identical, 
so  that  the  extra  heat  production  after  giving  fat  was  derived 
from  fat  itself. 

It  has  already  been  demonstrated  that  less  protein  is 
burned  in  starvation  when  the  body  is  fat  than  when  it  is  lean. 
It  would,  therefore,  seem  that  if  protein  and  fat  were  ingested 
together,  a  similar  reduction  in  the  amount  of  the  protein 
requirement  would  be  effected  (Voit). 

It  has  been  shown  in  a  previous  chapter  that  nitrogenous 
equilibrium  can  be  maintained  in  a  dog  only  after  the  ingestion 
of  three  and  a  half  times  the  quantity  of  protein  destroyed  in 
starvation  (seep.  154). 

E.  Voit  and  Korkunoff,1  continuing  these  experiments,  find 
that  if  fat  and  meat  be  ingested  together,  the  quantity  of  the 
latter  necessary  to  establish  nitrogenous  equilibrium  is  reduced 
to  between  1.6  to  2.1  times  the  starvation  minimum.  Much 
less  protein  food  is,  therefore,  required  to  maintain  the  body's 
protein  when  it  is  ingested  with  fat  than  when  it  is  given  alone. 

Thus  Thomas2  could  not  maintain  nitrogen  equilibrium 
when  twice  the  amount  of  the  fasting  nitrogen  elimination  was 
given  to  a  man  in  the  form  of  meat  alone,  but  was  able  to 
accomplish  this  when  meat  to  the  extent  of  that  destroyed  in 
fasting  was  administered  with  fat.  In  consequence  of  this, 
protein  is  more  readily  added  to  the  body  when  fat  is  ingested 
with  it,  as  is  seen  in  the  following  experiment  of  Rubner3  on  a 
man: 

1  Voit  and  Korkunoff:    "Zeitschrift  fiir  Biologie,"  1895,  xxxii,  117. 

2  Thomas:   "Archiv  fiir  Physiologie,"  1910,  Supplement,  p.  249. 

3  Rubner:  von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1903,  i,  43. 


THE   INFLUENCE    OF   THE    INGESTION   OF   FAT  255 

INFLUENCE    OF    FAT    INGESTION    ON    NITROGEN    RETENTION 


Food. 

N  Metabolism. 

N. 

Fat. 

Carbohydrates. 

N  in  Excreta. 

N  to  Body. 

23.6 

23-5 
23.0 

23-4 

99. 

195- 

214. 

350. 

260 
226 
221 
234 

26.36 
2i-55 
18.5 
17.6 

-3-64 
+  1.85 
+4-13 

+5-75 

With  increasing  quantities  of  fat  there  is  an  increasing 
addition  of  protein  to  the  body. 

It  has  already  been  shown  that  protein  ingested  alone  in 
large  quantity  establishes  nitrogen  equilibrium  at  a  higher 
level,  constantly  raising  the  amount  of  heat  produced  until 
nitrogenous  equilibrium  is  reached  (the  secondary  dynamic 
rise,  p.  233). 

The  same  destruction  of  the  easily  oxidized  protein  takes 
place  when  it  is  given  with  fat,  as  was  shown  by  Voit1  in  the 
following  experiment  on  a  dog: 

THE  "SECONDARY  RISE"  IN  PROTEIN  METABOLISM  ON  A  MEAT- 
FAT  DIET 


(Weights 

in  Grams.) 

Food. 

Meat. 

Fat. 

Urea. 

Flesh  to  Body 

1800 

O 

127.9 

26 

1S00 

O 

127.6 

26 

1800 

250 

117.9 

162 

1800 
1800 

250 
250 

"3-5l 

I20.7J 

171 

1800 
1800 

250 
250 

"5-71 
119.7/ 

164 

1800 
1800 

250 
250 

127-5! 
130.0/ 

11 

A  prolonged  deposition  of  protein  in  the  normal  adult, 
when  fat  is  given  with  it,  is  demonstrably  difficult. 

The  question  arises,  Does  the  ingestion  of  large  quantities 
of  fat  also  cause  an  increase  in  the  metabolism  until  fat  com- 
bustion is  balanced  by  its  ingestion? 

1  Voit:  Hermann's  Handbuch,  "Physiologie  des  Stoffwechsels,"  1881,  p.  131. 


256  SCIENCE    OF   NUTRITION 

Rubner1  has  shown  that  this  is  not  the  case.  He  cites  the 
record  of  the  following  long  respiration  experiment  on  a  dog 
which  was  given  80  grams  of  meat  and  30  grams  of  fat  daily: 

ABSENCE  OF  THE  "SECONDARY  DYNAMIC  RISE"  IN  FAT  METAB- 
OLISM  ON   A   MEAT-FAT   DIET 

(Fat  being  given  in  excess  of  the  requirement.) 
Calories  or  Metabolism. 


Protein. 

Fat. 

Total. 

97.2 

173.0 

270.0 

83.0 

178.0 

261. 1 

89-3 

173-5 

262.7 

85.6 

163.2 

248.9 

87.8 

169.0 

256.8 

83.0 

159.6 

242.6 

74-4 

I7I-7 

246.2 

78.0 

178.4 

256.3 

80.0 

179.6 

259-7 

The  diet  was  58.7  per  cent,  above  the  starvation  require- 
ment. It  contained  354  calories,  of  which  21.5  per  cent,  were 
in  protein.  The  mean  heat  production  during  the  period  of 
ingestion  of  food  was  256.0  calories,  and  in  the  following 
starvation  days  223.2  calories,  showing  an  increase  in  metab- 
olism of  1 1.2  per  cent,  caused  by  an  excess  in  food  of  58.7  per 
cent.  During  the  later  days  the  animal  was  in  nitrogenous 
equilibrium.  Notwithstanding  an  excess  of  fat  in  the  diet, 
and  a  continued  deposit  of  fat  in  the  body,  there  was  no  in- 
crease in  the  metabolism  during  the  time  of  experimentation. 
The  secondary  dynamic  action  noted  by  Rubner  as  regards 
protein  does  not,  therefore,  take  place  as  regards  fat.  The 
storage  of  fat  in  the  body  is  consequently  a  matter  of  com- 
parative ease. 

Rubner2  has  compared  the  metabolism  of  a  boy  who  was 
obese  with  that  of  his  brother,  who  was  a  year  older,  but  thin. 
They  were  the  children  of  parents  of  small  means  and  would 
not  naturally  be  overfed.  The  interesting  point  of  the  experi- 
ment was  whether  obesity  was  due  to  a  reduced  metabolism 
with  the  consequent  deposition  of  fat.  Each  boy  was  given 
a  maintenance  diet,  or  one  which  balanced  his  metabolism, 

1  Rubner:  "Energiegesetze,"  1902,  p.  251. 

a  Rubner:   "Beitrage  zur  Ernahrung  im  Knabenalter,"  1902. 


THE  INFLUENCE  OF  THE  INGESTION  OF  FAT     .257 

without  adding  to  or  subtracting  from  his  body  substance. 
The  general  results  are  as  follows: 

Fat  Boy.  Then  Boy. 

Age  in  years 10  11 

Weight  in  kilograms 41  26 

Total  calories  of  metabolism 1786. 1  1352. 1 

Calories  per  kilogram 43.6  52.0 

Calories  per  sq.  m.  surface 1321.  1290. 

The  comparison  shows  that  the  fat  brother  had  a  larger  total 
metabolism  than  the  thin  one,  but  the  fat  boy  also  had  the 
larger  surface.  Per  square  meter  of  surface  the  metabolism 
was  the  same  (see  p.  129).  The  gradual  increase  in  the  area 
of  the  body  caused  by  filling  out  the  fat  cells  may  therefore 
increase  combustion,  but  this  is  not  due  to  the  specific  action 
of  the  fat  on  metabolism  as  in  the  case  of  the  secondary 
dynamic  rise  after  protein  ingestion,  but  rather  to  the  in- 
crease in  the  size  of  the  body.  Carbohydrates,  which  in 
excess  are  converted  into  fat,  must  behave  in  the  same  way. 
It  will  be  noticed  that  in  the  experiment  where  80  grams  of 
meat  and  30  grams  of  fat  were  daily  ingested,  although  the  pro- 
tein metabolism  gradually  fell,  the  fat  metabolism  gradually 
rose,  and  in  isodynamic  relation  to  the  fall  in  protein.  Allow- 
ing for  the  difference  in  specific  dynamic  action,  protein  and 
fat  replace  each  other  in  metabolism  in  isodynamic  quantities. 
17 


CHAPTER  IX 

THE    INFLUENCE    OF  THE  INGESTION  OF  CARBO- 
HYDRATE 

PART  I— THE   INTERMEDIARY   METABOLISM 

The  preceding  chapters  have  dealt  entirely  with  the  sub- 
ject of  the  metabolism  of  protein  and  fat.  The  metabolism 
of  carbohydrate  has  been  touched  upon  incidentally  in  des- 
cribing the  intermediary  metabolism  of  protein,  but  the  fuller 
details  remain  to  be  considered.  Generally  speaking,  two- 
thirds  of  the  energy  produced  by  the  human  organism  is 
derived  from  the  oxidation  of  carbohydrate.  Not  without 
warrant  is  bread  considered  the  staff  of  life. 

Glycogen. — The  gastro-intestinal  tract  converts  starches 
into  glucose,  inverts  sucrose  into  glucose  and  fructose,  and 
lactose  into  glucose  and  galactose,  so  that  these  soluble  mono- 
saccharids  become  the  fuels  transported  by  the  blood  for  the 
nourishment  of  the  body-cells.  The  enzymes  maltase,  invertin, 
and  lactase  which,  respectively,  convert  maltose,  suchrose, 
and  lactose  into  monosaccharids,  are  present  in  the  intestinal 
mucosa  of  the  newborn  infant.1 

The  writer  personally  prepared  fructose  from  inulin  in 
1889,  which  when  given  to  a  fasting  rabbit  caused  the  for- 
mation in  its  liver  of  large  quantities  of  glycogen,  the  anhy- 
drid  of  glucose.2  To  a  lesser  extent  the  same  fate  may  be- 
fall ingested  galactose.  After  giving  glucose  or  fructose,  as 
much  as  40  per  cent,  of  the  dry  solids  of  the  liver  consisted 
of  glycogen.  These  monosaccharids  were  not  changed  in 
the  intestine. 

1  Ibrahim:   "Zeitschrift  fur  physiologische  Chemie,"  1910,  lxvi,  19. 

2  Voit:   "Zeitschrift  fur  Biologie,"  1891,  xxviii,  245. 

258 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   259 

Isaac1  perfused  a  fluid  made  up  of  washed  dog's  blood-cells 
and  Ringer's  solution  containing  fructose  through  the  liver 
of  a  fasting  dog  and  found  that  the  fructose  was  converted 
into  glucose.  The  change  in  the  composition  of  the  per- 
fusing fluid  was  as  seen  below: 

Before  Perfusion.       Three  Hours  Later. 

d-Glucose 0.012  per  cent.  0.310  per  cent. 

d-Fructose 0.349       "  0.020       " 

Ishimori2  has  reported  that  glycogen  deposition  in  the 
liver  follows  the  intravenous  injection  of  glucose  and  fructose 
in  the  rabbit,  although  galactose  does  not  have  this  effect. 
Galactose  is  less  readily  oxidized,  at  least  in  the  adult  organ- 
ism, than  are  the  other  two  hexoses  (see  p.  294),  though  it 
may  be  that  the  conditions  for  its  breakdown  are  more  favor- 
able in  the  suckling. 

The  quantity  of  glycogen  present  in  a  living  animal  can- 
not be  accurately  estimated.  Schondorff3  gave  seven  dogs 
diets  rich  in  carbohydrate  for  several  days,  and  found  that  the 
quantity  of  glycogen  present  in  their  bodies  varied  between 
7.59  and  37.87  grams  per  kilogram. 

The  distribution  of  this  glycogen  in  100  grams  of  the  fresh 
tissue  varied  as  follows : 

Maximum.  Minimum. 

Liver 18.69  7-3 

Muscle 3.72  0.72 

Heart 1.32  0.104 

Bone 1.90  0.197 

Intestines 1.84  0.026 

Skin, 1.68  0.09 

Brain 0.29  0.047 

Blood 0.0066  0.0016 

The  traditional  distribution  of  glycogen,  one-half  to  the  liver 
and  one-half  to  the  rest  of  the  body,  Schondorff  shows  to  be 
incorrect.  For  100  grams  of  liver  glycogen  there  occurred  in 
the  rest  of  the  body  the  following  amounts : 

1  Isaac:   "Zeitschrift  fiir  physiologische  Chemie,"  1914,  Ixxxix,  78. 

2  Ishimori:    "Biochemische  Zeitschrift,"  1912-13,  xlviii,  332. 

3  Schondorff:  "Pfliiger's  Archiv,"  1903,  xcix,  191. 


260  SCIENCE    OF    NUTRITION 

Dog       1 398  grams. 


II 


279 


HI 87      " 

IV 76     << 

V 159     " 

VI 355      « 

VII 105      " 

It  is  an  interesting  observation  of  Kiilz1  and  of  Jensen2 
that  an  active  organ  like  the  heart  maintains  its  normal 
glycogen  content  even  after  fifteen  days  of  starvation. 

In  the  various  discussions  on  the  subject  of  glycogen  it  has 
been  shown  that  in  starvation,  and  after  protein  and  sugar  in- 
gestion, there  is  glycogen  present  in  the  body — a  constant 
supply  always  ready  for  emergencies,  which  can  be  reduced 
through  exercise,  but  which  is  only  to  be  completely  removed 
by  tetanic  convulsions  (pp.  107  and  457). 

The  writer  has  here  avoided  the  discussion  of  a  production 
of  sugar  from  fat.  To  his  mind  the  evidence  is  against  such 
production,  as  will  be  demonstrated  in  the  chapter  on  Diabetes. 

THE  INTERMEDIARY  METABOLISM  OF  CARBOHYDRATE 

The  chemical  transformations  of  sugar  molecules  present 
a  fascinating  field  for  the  explorer.  It  is  only  possible  to 
indicate  here  some  of  the  scientific  facts  which  are  leading  to  a 
correct  understanding  of  the  subject.  There  is  some  un- 
avoidable repetition  of  the  facts  presented  in  the  chapter  on 
The  Intermediary  Metabolism  of  Protein. 

Lobrey  de  Bruyn  and  van  Eckenstein3  found  that  when 
glucose  solutions  contained  mere  traces  of  hydroxyl  ions, 
d-mannose,  d-fructose,  and  d-pseudo-fructose  appeared,  and 
this  phenomenon,  called  miliar otation,  continued  until  the 
solution  no  longer  rotated  polarized  light.  Other  hexoses 
have  since  been  discovered  in  the  mixture.  According  to 
Nef4  any  ordinary  hexose  can  yield  116  different  substances. 
Of  these,  he  was  able  to  identify  93,  of  which  47  were  sugars 

1  Kiilz:   "Festschrift  zu  Ludwig,"  1891,  p.  109. 

2  Jensen:    "Zeitschrift  fur  physiologische  Chemie,"  1902,  xxxv,  525. 

3  Lobrey  de  Bruyn  and  van  Eckenstein:  "Receuil  des  travaux  chimiques 
des  Pay-Bas,"  1895,  xiv,  158,  203;  1899,  xix>  *■ 

4  Nef:  "Annalen  der  Chemie  und  Pharmacie,"  1907,  ccclvii,  214. 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   26 1 


and  the  rest  fragments  of  sugar  cleavage.  Henderson1  finds 
a  slow  but  unmistakable  loss  of  optical  activity  in  a  glucose 
solution  maintained  at  the  body  temperature  and  at  the  al- 
kalinity of  the  blood,  though  the  quantity  of  sugar  present  is 
not  affected. 

Nef2  suggests  that  the  reaction  d-fructose  — ►  glucose 
must  take  place  through  the  intermediary  formation  of  an 
enol.     This  may  be  written  as  follows: 

CH2OH  CHOH  HCO 


CO 


HOCH 


HCOH 


COH 


HOCH 


HCOH 


HCOH 


OHCH 


HCOH 


HOCH 

|\ 

HCOH\ 


0 


OHCH 


HC 


HCOH 


HCOH 


HCOH 


HCOH 


CH2OH 

d-Fructose. 


CH,OH 

Enol  form. 


CH2OH 

d-GIucose. 


CHoOH 

d-Glucose.3 


Glucose  behaves  like  a  very  weak  acid.  In  the  presence 
of  alkali,  mutarotation  with  the  production  of  various  isomeric 
forms  is  possible.  The  presence  of  traces  of  acid  prevents 
these  transformations  as  well  as  any  oxidative  changes.  To 
the  invulnerability  of  the  glucose  molecule  under  these 
circumstances  has  been  ascribed  its  non-destruction  in 
diabetes  (see  p.  485).  An  increase  in  the  hydrogen  ion  con- 
centration of  a  perfusing  fluid  greatly  reduces  the  utilization 
of  glucose  by  an  excised  beating  heart.4 

The  analogy  between  the  phenomenon  of  Lobrey  de  Bruyn 
and  the  reactions  which  take  place  in  the  body  is  incomplete  in 
that  the  latter  always  occur  in  one  direction.  Glucose,  for 
example,. is  not  converted  into  fructose  within  the  organism. 

1  Henderson,  L.  J.:    "Journal  of  Biological  Chemistry,"  ion,  x,  3. 

2  Nef:    "Annalen  d.  Chemie  und  Pharmacie,"  1907,  ccclvii,  294. 
3Tollen's  formula,  accepted  by  Emil  Fischer:     "Berichte  der  d.  chem. 

Gessellschaft,"  191 2,  xlv,  461. 

4Rona  and  Wilenko:    "Biochemische  Zeitschrift,"  1913-14,  lix,  173. 


262 


SCIENCE   OF    NUTRITION 


Nef  believes  that  the  many  chemical  reactions  of  sugar 
may  be  best  explained  on  the  assumption  that  the  sugar  is  in 
part  dissociated,  giving  residues  which  may  be  synthesized 
into  glucose  again.  Such  substances  might  be  glyceric 
aldehyd  or  methylglyoxal  (see  p.  193).  Fragments  of  this 
sort  might  be  open  to  ready  oxidation  in  the  body,  or  be  for 
use  as  the  food  of  yeast  cells  in  alcoholic  fermentation.  When 
glucose  or  its  hypothetic  cleavage  products,  glyceric  aldehyd 
or  methylglyoxal,  are  treated  with  alkali  in  the  presence  of 
oxygen  they  are  oxidized  to  carbon  dioxid  and  water.  If  no 
oxygen  is  present,  lactic  acid  appears  in  the  solution.  But  if 
lactic  acid  be  added  to  an  oxygenated  alkaline  solution  of 
glucose,  lactic  acid  is  not  destroyed.  Hence,  in  the  oxidative 
destruction  of  glucose,  lactic  acid  in  not  an  intermediary 
product.1 

The  relations  between  the  trioses  or  sugars  containing 
three  carbon  atoms  and  substances  into  which  they  are 
convertible  are  shown  below.  All  of  these  substances  when 
given  to  a  phlorhizinized  dog  are  completely  converted  into 
glucose: 


HCHOH 

HCO 

HCO 

HCHOH 

HCOH 

HCOH 

OHCH 

CO 

HCHOH 
Glycerol 
(alcohol). 

HCHOH 

d-Glyceric 
aldehyd 
(aldose). 

HCHOH 

1-Glyceric 
aldehyd 
(aldose). 

HCHOH 

Dioxy  acetone 

(ketose) . 

HOCO 

HCO 

1 

HOCO 

HOCO 

HCOH 

CO 

HCOH 

HOCH 

HCHOH 

d-Glyceric  acid. 

CH3 

Methylglyoxal. 

CH3 

d-Lactic  acid. 

CH3 

1-Lactic  acid. 

Mandel  and  Lusk2  gave  lactic  acid  to  a  phlorhizinized 
dog  and  found  it  was  eliminated  as  extra  glucose  in  the  urine 
(see  p.  191).     They  furthermore  found  that  the  d-lactic  acid 

1  This  description  is  taken  from  Woodyatt:  "Well's  Chemical  Pathology," 
2d  ed.,  1914,  p.  578. 

2  Mandel,  A.  R.,  and  Lusk:  "American  Journal  of  Physiology,"  1906,  xvi, 
129. 


INFLUENCE    OF    THE    INGESTION    OF    CARBOHYDRATE      263 

which  is  eliminated  in  the  urine  of  dogs  poisoned  with  phos- 
phorus disappears  from  such  urine  after  the  administration  of 
phlorhizin.  They,  therefore,  concluded  that  lactic  acid  arose 
from  the  metabolism  of  glucose,  and  that  when  glucose,  its 
antecedent  substance,  was  removed  by  phlorhizin,  lactic  acid 
vanished  from  the  urine.  They  proposed  the  following  formula 
of  carbohydrate  metabolism: 

lactic  acid     <  ~^_    glucose     ^ glycogen 

Embden1  had  previously  shown  that  d-lactic  acid  arises 
through  the  artificial  perfusion  of  a  liver  which  is  rich  in 
glycogen. 

Von  Fiirth2  has  confirmed  this  work  by  demonstrating  that 
the  quantity  of  lactic  acid  eliminated  in  phosphorus-poisoning 
is  increased  after  administering  glucose.  He  further  showed 
that  the  lactic  acid  elimination  which  occurs  after  cooling 
rabbits  is  increased  if  carbohydrate  be  ingested,  and  is  pre- 
vented if  the  animal  be  freed  from  carbohydrate  by  means  of 
adrenalin.  He,  therefore,  concludes  that  lactic  acid  un- 
questionably arises  from  glucose. 

Of  similar  import  are  the  experiments  of  Sass,3  who  showed 
that  when  strychnin  convulsions  were  induced  in  dogs 
rendered  diabetic  by  pancreas  extirpation,  though  the  con- 
vulsions were  more  powerful  than  in  normal  animals,  there 
was  no  lactic  acid  formation. 

d-Lactic  acid  is  always  found  in  the  normal  blood  and 
muscle.  Von  Fiirth4  states  that  there  are  between  350  and  550 
milligrams  of  lactic  acid  in  100  grams  of  fresh  normal  muscle  of 
man,  horse,  dog,  and  ox. 

When  a  muscle  dies  either  through  heat  or  natural  rigor 
mortis,  lactic  acid  is  produced  from  carbohydrate  within  the 
muscle.     Carbon  dioxid  is  driven  out  at  the  same  time,  on 

1  Embden:   "Centralblatt  fur  Physiologie,"  1904,  xviii,  832. 

2  von  Fiirth:    "Biochemische  Zeitschrift,"  1914,  lxiv,  131;  Ibid.,  156. 

3  Sass:  "Zeitschrift  fur  experimentelle  Pathologie  und  Therapie,"  1914,  xv, 
37o. 

4  von  Fiirth:   "Biochemische  Zeitschrift,"  1915,  lxix,  199. 


264  SCIENCE   OF   NUTRITION 

account  of  the  acid  production.1  Parnas  and  Wagner2  noticed 
that  mechanical  damage  to  frog's  muscle  caused  the  formation 
of  lactic  acid  without  a  decrease  in  the  carbohydrate  content. 
This  appears  to  confirm  the  lactacidogen  theory  of  Embden3, 
who  found  that  a  press  juice  derived  from  muscle  formed  lactic 
acid  apparently  from  some  unknown  compound,  though  it 
left  untouched  added  glucose,  glycogen,  or  d-1-alanin.  This 
substance  is  very  likely  methylglyoxal.4  Perhaps  much  of 
the  lactic  acid  found  in  tissue  is  formed  postmortem  from 
methylglyoxal. 

Levene  has  accomplished  a  large  amount  of  work  upon  the 
intermediary  metabolism  of  carbohydrate.  He5  reported  that 
leukocytes  suspended  in  a  Henderson  phosphate  mixture 
containing  glucose  induced  glycolysis  with  the  formation  of 
d-lactic  acid  only,  and  without  evidence  of  oxidation.  This 
work  has  been  confirmed  by  others,6  who  have  shown  that 
glycolysis  in  the  shed  blood  is  nothing  more  than  the  conver- 
sion of  glucose  into  lactic  acid.  Oppenheimer7  reports  a  rapid 
formation  of  d-lactic  acid  when  d-fructose  is  added  to  a  per- 
fusing fluid  and  passed  through  a  surviving  liver. 

Levene  and  Meyer8  found  further  that  leukocytes  formed 
lactic  acid  from  d-glucose,  d-mannose,  and  d-galactose,  and 
that  kidney  tissue  caused  a  formation  of  lactic  acid  from 
d-glucose,  d-fructose,  and  d-mannose. 

The  reactions  which  lead  to  the  production  of  d-lactic 
acid  from  the  various  hexoses  necessitate  the  presence  of  an 
intermediate  substance,  otherwise  d-1-lactic  acid  would  fre- 
quently be  the  end-product. 

1  Fletcher  and  Brown:   "Journal  of  Physiology,"  1914,  xlviii,  177. 

2  Parnas  and  Wagner:    "Biochemische  Zeitschrift,"  1914,  lxi,  387. 

3  Embden,  Kalberlah,  and  Engel:  Ibid.,  191 2,  xlv,  45;  Embden,  Griesbach, 
and  Schmitz:  "Zeitschrift  fur  physiologische  Chemie,"  1914-15,  xciii,  1. 

4Neuberg:   "Biochemische  Zeitschrift,"  1913,  xlix,  505. 

B  Levene  and  Meyer:  "Journal  of  Biological  Chemistry,"  1912,  xi,  361; 
191 2,  xii,  265. 

6Kraske:  "Biochemische  Zeitschrift,"  1912,  xlv,  81;  Kondo:  Ibid.,  p.  88; 
von  Noorden,  Jr.:   Ibid.,  94. 

7  Oppenheimer:   "Biochemische  Zeitschrift,"  191 2,  xlv,  30. 

8  Levene  and  Meyer:  "Journal  of  Biological  Chemistry,"  1913,  xiv,  149,  and 
ibid.,  xv,  65. 


INFLUENCE   OF   THE   INGESTION   OF    CARBOHYDRATE      265 

Wohl1  refers  to  the  fact  that  methylglyoxal  in  alkaline 
solution  is  convertible  into  lactic  acid.  This  has  been  shown 
to  take  place  in  tissue  by  Dakin2  and  by  Neuberg,3  and  to  be 
induced  by  white  blood-cells.4 

The  three  trioses,  d-  and  1-glyceric  aldehyd  and  dioxy- 
acetone,  yield  lactic  acid  when  treated  with  alkali.5  When 
the  red  blood-cells  of  cattle  are  brought  into  a  glucose  solution 
they  have  no  glycolytic  effect;  however,  they  do  change 
d-l-gly eerie  aldehyd  and  dioxyacetone  into  d-1-lactic  acid.6 
Solutions  of  these  cells  have  no  effect  on  glucose,  but  convert 
d-l-gly  eerie  aldehyd  into  d-1-lactic  acid.  This  suggests  the 
possibility  of  glyceric  aldehyd  being  an  intermediate  metab- 
olite of  glucose. 

Embden7  has  especially  emphasized  this  method  of  sugar 
metabolism,  and  pictures  the  cleavage  of  glucose  and  fructose 
as  follows: 


0 

11 

C— H 

0 

II 

C— H 

CH2OH 

1 

CH2OH 

H— C— OH 

> 

H— C— OH 

c  =  0 

>           C  =  0 

HO— C— H 

, 

CH2OH 

HO—  C— H 

CH2OH 

1 
H— C— OH 

H— C— OH 

1  XH 
H— C— OH 

1 

H— C— OH 
II— C— OH 

1  XH 
►    H— C— OH 

CH2OH 

d-Glucose. 

CH2OH 

d-Glyceric  aldehyd. 

CH2OH 

d-Fructose. 

CH2OH 

Dioxyaceton; 
d-glyceric  aldehyd. 

One  may  also  conceive  of  the  breakdown  of  glucose  into 
one  molecule  of  glyceric  aldehyd  and  one  of  methylglyoxal, 
or  into  two  molecules  of  methylglyoxal,  as  shown  below: 


1  Wohl:    "Biochemische  Zeitschrift,"  1907,  v,  45. 

2  Dakin  and  Dudley:   "Journal  of  Biological  Chemistry  "  1913,  xiv,  155. 

3  Neuberg:  "Biochemische  Zeitschrift,"  1913,  xlix,  502. 

4Levene  and  Meyer:    "Journal  of  Biological  Chemistry,"  1913,  xiv,  551. 
6  Oppenheimer:    "Biochemische  Zeitschrift,"  1912,  xiv,  134. 

6  Embden,  Baldes,  and  Schmitz:  Ibid.,  1912,  xiv,  108. 

7  Embden,    Schmitz,    and    Wittenberg:      "Zeitschrift   fur   physiologische 
Chemie,"  1913,  lxxxviii,  210. 


266 


SCIENCE   OF 

NUTRITION 

CHO 

CHO 

CHO 

CHO 

HCOH 

1 

H 

COH 

|| 

HCOH 

I 

H 

COH 

|| 

30CH 

OH 

CH2 

HOCH 

OH 

CH2 

HCOH 

CHO 

HCOH 

► 

CHO 

• 

HCOH 

HCOH 

HCOH 

H 

COH 

II 
CH2 

Methylglyoxal. 

CH2OH 

d-Glucose. 

CH2OH 

Methylglyoxal. 
d-Glyceric  aldehyd. 

CH2OH 

d-Glucose. 

OH 

The  production  of  methylglyoxal  (CH3.CO.CHO  or  CH2  : 
COH.  CHO)  as  an  intermediary  metabolite  of  sugar  metab- 
olism is  of  theoretic  importance  as  showing  by  what  means 
the  asymmetry  of  the  central  carbon  atom  of  a  triose  like 
d-l-gly eerie  aldehyd  may  be  abolished,  and  then  through  the 
determinative  influence  of  living  cells  be  transmuted  into  a 
d-compound  (Dakin,  see  p.  193). 

It  will  be  shown  later  that  lactic  acid  appears  in  the 
urine  in  many  asphyxial  conditions  (see  p.  422),  and  the  long 
series  of  experiments  which  have  been  very  briefly  referred  to 
above  have  been  performed  under  asphyxial  conditions.1 
Only  under  these  circumstances  can  the  Cannizzaro  reaction 
(see  p.  192)  take  place. 


CH3 

I 
CO 

I 

CHO 

Methylglyoxal. 


0 


CH3 

HCOH 

I 

COOH 

Lactic  acid. 


The  experiments  described  above  indicate  that  lactic  acid 
is  not  oxidized  when  formed.  It  is,  therefore,  highly  probable 
that  it  must  first  be  synthesized  to  glucose,  or  at  least  undergo 
reversible  conversion  into  methylglyoxal  which  is  convertible 
into  glucose  (see  p.  193)  before  it  can  undergo  oxidation. 

After  consideration  of  all  the  evidence  at  hand,  Dakin2 
presents  "the  construction  of  a  crude  scheme  aiming  at  the 

1  Woodyatt:   "Well's  Chemical  Pathology,"  1914,  p.  579. 

2  Dakin:  "XVIIth  International  Congress  of  Medicine,"  London,  Subsec- 
tion Ilia,  1913,  p.  105. 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   267 

representation  of  the  biochemical  interconversions  of  alanin, 
lactic  acid,  methylglyoxal,  glyceric  aldehyd,  and  glucose." 
(Details,  pp.  192-193.) 

Glycogen 

T   I 
I  i 

Glucose 
(C6H1206) 

T  I 
I  i 

Glyceric  aldehyd 
(C6H603) 

T  I 

Lactic  acid  Methylglyoxal  Alanin 

(CH3CHOHCOOH)       (CH3CO.CHO)  (CH3CHNH2COOH) 

The  question  of  the  further  fate  of  methylglyoxal  in  the 
organism  is  uncertain.  It  is  known  from  the  work  of  Neu- 
berg1  that  carboxylase,  which  exists  within  the  living  yeast 
cell,  splits  pyruvic  acid  into  acetaldehyd  and  carbon  dioxid, 
the  acetaldehyd  being  then  either  oxidized  to  acetic  acid  or 
reduced  to  alcohol. 

Levene  and  Meyer2  find  that  leukocytes  and  kidney 
tissue  will  not  cause  the  cleavage  of  pyruvic  acid  into  acet- 
aldehyd and  carbon  dioxid  nor  oxidize  it  either,  so  that 
when  one  comes  to  consider  the  ultimate  fate  of  glucose  in  the 
organism  the  question  is  beset  with  difficulties,  for  the  destruc- 
tion of  glucose  depends  on  oxidative  processes  which  take  place 
within  the  living  cell  and  which  are  not  to  be  reproduced 
without  the  living  structure.  One  can  only  formulate  a 
hypothesis  that  acetaldehyd  is  a  cleavage  product  of  car- 
bohydrate, as,  indeed,  was  postulated  by  Magnus-Levy3  while 
working  in  Hofmeister's  laboratory.  From  methylglyoxal, 
acetaldehyd  might  arise  as  follows : 

CH3        CH3        CH3        HCOOH 
CO     H     CHO         COOH        HCOOH 

!     !    

CHO    OH    HCOOH 

1  Neuberg:   "Biochemische  Zeitschrift,"  ion,  xxxvii,  170. 

2  Levene  and  Meyer:    "Journal  of  Biological  Chemistry,"  1914,  xvii,  443. 

3  Magnus-Levy:    "Archiv  fur  Physiologie,"  1902,  p.  365. 


268 


SCIENCE   OF   NUTRITION 


In  the  presence  of  oxygen  acetaldehyd  would  be  oxidized 
to  acetic  acid,  which  is  not  convertible  into  glucose,  and  this 
would  then  be  oxidized  to  formic  acid  which  readily  breaks  up 
into  carbon  dioxid  and  water  (see  p.  302).  In  the  presence  of 
hydrogen,  acetaldehyd  is  reduced  to  alcohol. 


CH3 

I 

CHO 


+     H2 


CH3 
CH2OH 


This,  however,  cannot  take  place  to  any  considerable 
extent  in  the  organism,  for  in  asphyxial  conditions  lactic  acid 
is  the  end-product  of  glucose  breakdown,  and  from  it  alcohol 
cannot  be  evolved.  The  production  of  alcohol  from  carbo- 
hydrate in  metabolism  is  thus  automatically  checked. 

The  formation  of  fat  from  carbohydrate  when  it  is  given 
in  excess  is  probably  due  to  the  condensation  of  aldehyd 
molecules  (Magnus-Levy) .    The  process  may  thus  be  pictured : 


CH3 

CH3 

CHO 

HCOH 

CH3 

I 
CHO 

CH2 
CHO 

CH3 

CH3 

1 

CO 

H 

CHO 

CHO 

OH 

HCOOH 

Ha 


CH3 
I 
CH2 

CH2 

HCOH 

I 
CH2 

CHO 


CH3 

I 
CH2 

I 
CH2 

CH2 

CH2 

I 

COOH 


C02 

If  at  any  time  the  aldehyd  radicle  at  the  end  of  the  chain 
becomes  oxidized,  the  fatty  acid  is  completed  and  the  process 
of  addition  terminates.  In  this  fashion  through  condensa- 
tion of  acetaldehyd  radicles  split  from  methylglyoxal,  fatty 
acids  with  even  numbers  of  carbon  atoms  may  be  synthesized 
from  carbohydrate  in  the  animal  organism. 

Written  in  its  simplest  form  the  production  of  palmitic 
acid  from  glucose  would  appear  as  follows: 


4C6H1206  =  C16H3202  +  2HCOOH  +  6C02  +  6H20 


INFLUENCE    OF   THE   INGESTION   OF    CARBOHYDRATE      269 

The  end-result  is  one  of  carbon  dioxid  cleavage,  just  as  in  the 
case  of  the  alcoholic  fermentation  of  pyruvic  acid  induced  by 
yeast  cells. 

To  enter  still  deeper  into  the  part  played  by  yeast  cells, 
and  to  discuss  in  detail  the  notable  and  fascinating  work  of 
Carl  Neuberg,  would  carry  one  beyond  the  object  of  this  book.1 

The  various  sugars  diffuse  rapidly  in  the  body.  Thus 
when  milk-sugar,  which  cannot  be  oxidized  by  the  organism,  is 
introduced  intravenously  into  a  dog,  after  half  an  hour  75  per 
cent,  of  the  quantity  present  in  the  animal  is  found  in  the 
tissues  and  only  25  per  cent,  in  the  blood.2  The  entrance  of 
glucose  into  the  cells  by  diffusion  is  accelerated  by  increasing 
their  temperature.3 

THE   INFLUENCE   OF  CARBOHYDRATE  ON  PROTEIN  METAB- 
OLISM AND  PROTEIN  RETENTION 

At  the  suggestion  of  Voit,  who  believed  that  the  sudden 
withdrawal  of  carbohydrate  from  the  food  would  increase 
protein  metabolism  and  would  explain  the  high  tissue  waste  in 
diabetes,  Lusk4  established  himself  in  nitrogen  equilibrium 
at  two  different  levels.  Withdrawal  of  350  grams  of  carbo- 
hydrate from  the  diet  increased  the  protein  metabolism  as 
appears  below.  The  losses  of  body  nitrogen  are  greater  for 
the  second  day  of  change  in  the  diet  than  for  the  first,  since 
the  metabolism  at  first  remains  under  the  influence  of  an  ample 
glycogen  supply  which  is  available  as  a  source  of  carbohy- 
drate (see  p.  72). 

1  Consult  Neuberg:  "Oppenheimer's  Handbuch  der  Biochemie,"  Ergan- 
zungsband,  1913,  p.  569;  Neuberg:  "Biochemische  Zeitschrift,"  1915,  bad,  1; 
v.  Euler:  "Neure  Forschung  iiber  alkoholische  Gahrung,  Fortschritte  der  Natur- 
wissenschaftlichen  Forschung,"  1914,  x,  63. 

2  Schwarz  and  Pulay:  "Zeitschrift  fur  exp.  Path,  und  Ther.,"  1915,  xvii, 
383- 

3  Masing:    "Pfliiger's  Archiv,"  1914,  clvi,  401. 

4  Lusk:   "Zeitschrift  fur  Biologie,"  1890,  xxvii,  459. 


270 


SCIENCE    OF   NUTRITION 


INFLUENCE  OF   CARBOHYDRATE    WITHDRAWAL  ON   PROTEIN 

METABOLISM 


Exp. 

Days  of 
Experi- 
menta- 
tion. 

Food. 

Ex- 
Creta 

N. 

TO 

Body. 

Remarks. 

No. 

Calor- 
ies. 

N. 

I 

II 

Ii  2,3 

1 

2,3 

2 
1 

2 

2953 
1078 
1078 

2490 
015 
6i5 

20.SS 
20.55 
20.55 

9-23 
9-23 

9-25 

19.84 
23.78 
27.OO 

13.08 

13-27 
17.18 

+0.71 
~3-23 
-6-45 

-3-85 
-4.04 

-7-95 

With  carbohydrate. 
Without  carbohydrate. 
Without  carbohydrate. 

With  carbohydrate. 
Without  carbohydrate. 
Without  carbohydrate. 

These  results  may  be  compared  with  the  later  results  of 
Thomas  (see  p.  155),  who  showed  that  protein  containing  18.4 
grams  of  nitrogen  when  given  to  a  man  did  not  maintain  the 
body  in  nitrogen  equilibrium  when  no  carbohydrate  was 
administered. 

Tallqvist1  found  that  partial  replacement  of  carbohydrate 
by  fat  in  the  diet  may  have  no  influence  or  only  a  transitory 
one  upon  the  amount  of  protein  metabolized.  Thus,  after 
establishing  nitrogen  equilibrium  in  man  with  a  diet  containing 
about  16  grams  of  nitrogen,  10  per  cent,  of  the  calories  being 
in  protein  and  90  per  cent,  in  carbohydrate,  he  replaced 
one-third  of  the  carbohydrate  calories  with  an  isodynamic 
quantity  of  fat  and  obtained  nitrogen  equilibrium  on  the  third 
day  of  the  diet.     This  is  of  value  in  practical  dietetics. 

Zeller2  gave  to  a  man  a  daily  diet  which  contained  very 
little  protein  and  between  2700  and  3300  calories  divided  into 
different  percentages  of  carbohydrate  and  fat.  The  protein 
metabolism  of  the  body  was  not  significantly  altered  until  less 
than  10  per  cent,  of  the  total  calories  were  given  in  the  form 
of  carbohydrate,  i.  e.,  butter,  360  grams;  sugar,  70  grams; 
sauerkraut,  300  grams;  tomatoes,  100  grams,  containing 
3300  calories.  At  this  juncture,  when,  as  Zeller  notes,  one 
molecule  of  monosaccharid  is  present  for  two  of  fat  in  the 

1  Tallqvist:   "Archiv  fur  Hygiene,"  1902,  xli,  177. 

2  Zeller:   "Archiv  fur  Physiologie,"  1914,  p.  213. 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   271 


diet,  aceton  appeared  in  the  urine  in  traces.  When  5  per 
cent,  of  the  calories  were  given  in  carbohydrate,  aceton 
appeared  abundantly  in  the  urine,  and  when  the  whole  of  the 
diet  consisted  of  fat  calories  there  was  a  still  higher  aceton 
excretion,  with  an  increasing  ammonia  production  to  neutralize 
the  acid  formed  and  the  patient  complained  of  weakness  and 
discomfort. 

The  following  table  epitomizes  the  results  obtained: 


Food. 

Urine  N 
Grams. 

Calories  in 

Per  Cent. 

Urine  N  per  ioo  Grams. 
N  in  Body  Grams. 

N  Grams. 

Carbohydrate. 

Fat. 

3-43 

IOO 

O 

5.i8 

0.16 

3.21 

75 

25 

5-75 

0.18 

3-27 

50 

50 

5.60 

0.17 

3.88 

25 

75 

4.82 

O.I5 

0.87 

10 

QO 

5-04 

0.16 

0.86 

5 

95 

6.02 

0.20 

1 .41 

0 

IOO 

6.90 

0.24 

3-43 

IOO 

0 

4-85 

0.15 

If  two  molecules  of  fat  are  oxidized  in  the  presence  of  one 
molecule  of  glucose  (which  assumes  that  the  3300  calories 
contained  in  the  diet  were  liberated  in  metabolism),  then  one 
molecule  of  fat  would  be  oxidized  in  the  presence  of  one  dis- 
sociated triose  molecule.  Each  molecule  of  fat  is  made  up  of 
one  molecule  of  gylcerin  and  three  of  fatty  acid.  Since 
glycerin  is  convertible  into  a  triose,  it  is  apparent  that  from 
glycerin  and  ingested  sugar  two  molecules  of  triose  are 
available  for  simultaneous  oxidation  when  three  of  fatty  acid 
are  burned.  Besides  this,  a  small  number  of  triose  molecules 
may  be  derived  from  protein  metabolized  and  another  quota 
from  stored  glycogen.  It  appears  from  this  analysis  possible 
that  the  normal  combustion  of  fat  each  molecule  of  /5-oxy- 
butyric  acid,  which  is  the  end-product  of  the  oxidation  of  each 
fatty  acid,  requires  the  presence  of  a  triose  molecule.     Under 


272  SCIENCE   OF   NUTRITION 

these  conditions  the  oxidation  of  fat  would  take  place  with- 
out acidosis  and  without  increasing  the  metabolism  of  protein. 

It  is  too  early  as  yet  to  give  a  satisfactory  explanation  of 
the  chemical  reactions  which  might  accompany  this  phenom- 
enon. It  may  be  noted  that  when  protein  is  given  in  large 
quantity  with  fat  the  acidosis  does  not  appear.  This  is 
understandable  in  view  of  the  production  of  glucose  from 
protein.  One  may  also  marvel  at  the  fact  that  the  "bread 
cards"  issued  in  Vienna  during  the  great  war  for  50  grams  of 
bread  daily  per  inhabitant  can  yield  scarcely  sufficient  car- 
bohydrate to  prevent  the  occurrence  of  acidosis  were  bread  the 
only  food. 

Zeller's  experiments  verify  the  conclusion  that  when  the 
protein  metabolism  is  reduced  to  a  minimum,  the  elimination 
of  creatinin  nitrogen  constitutes  about  20  per  cent,  of  the  total 
quantity  of  urinary  nitrogen  (see  p.  209) . 

A  significant  fact  is  that  when  the  body  changes  from  a 
carbohydrate  diet  to  one  of  fat  or  protein  there  is  a  consider- 
able loss  of  water.  This  was  first  noted  by  Bischoff  and  Voit,1 
who  gave  bread  to  a  dog  forty-one  days  and  witnessed  a  loss 
in  body  weight  of  531  grams,  although  if  the  nitrogen  elimina- 
tion of  the  period  had  been  all  attributed  to  muscle  breakdown 
the  loss  in  body  weight  should  have  been  over  3700  grams. 
Then  when  1800  grams  of  meat  were  given  in  quantity 
sufficient  to  cause  protein  deposit,  the  weight  of  the  animal 
fell  310  grams  on  the  first  day  of  this  diet. 

The  phenomenon  also  occurs  in  man,  as  the  following 
experiment  of  Benedict  and  Milner2  demonstrates.  The 
experimental  period  lasted  six  days,  mechanical  work  was 
performed  daily,  and  isodynamic  quantities  of  food,  which 
were  somewhat  under  the  nee.ds  of  the  body,  were  ingested. 
During  the  first  three  days  66  per  cent,  of  the  energy  in  the  food 
was  contained  in  carbohydrates,  and  during  the  last  three 

1  Bischoff  and  Voit:  "Gesetze  der  Ernahrung  des  Fleischfressers,"  i860, 
pp.  211  and  214. 

2  Benedict  and  Milner:  "U.  S.  Dept.  of  Agriculture,"  Office  of  Experiment 
Stations,  1907,  Bull.  175,  p.  224. 


INFLUENCE    OF   THE   INGESTION   OF    CARBOHYDRATE      273 

days  67  per  cent,  of  the  energy  was  in  the  form  of  fat.     The 
following  changes  were  noted: 

Carbohydrate 

Diet.  Fat  Diet. 

Daily  change  water  content  of  body,  grams .  .   +165  —906 

Daily  change  in  body  weight,  grams -j-  61  —914 

A  loss  of  body  glycogen  is,  therefore,  associated  with  a  loss 
of  body  weight. 

If  carbohydrates  be  ingested  alone,  immediately  after 
starvation,  the  protein  metabolism  may  fall  below  the  star- 
vation amount. 

This  higher  protein-sparing  property  gives  to  dogs  fed  on 
carbohydrates  alone  a  longer  lease  of  life  than  is  granted  to 
those  fed  on  fat  alone,  although  the  ultimate  outcome  is  the 
same. 

The  protein  metabolism  may  be  reduced  to  one-third 
the  fasting  value,  a  result  also  obtained  by  Landergren1  and 
by  Folin2  in  man.  Cathcart3  gave  a  man  who  had  been  fasting 
fourteen  days  a  diet  of  cream  (300  c.c.)  and  starch  (400  grams). 
The  nitrogen  excretion  in  the  urine  was  as  follows: 

Total  N.  Urea  N. 

Day  14  of  starvation 7.78  5.99 

"        1  on  cream-starch  diet 7.43  5.80 

"       2                  "              "   3.58  2.29 

"       3                  "              " 2.84  1.76 

The  absence  of  a  fall  in  protein  metabolism  on  the  first  day 
is  probably  to  be  explained  by  assuming  a  large  deposit  of 
glycogen  within  the  body  at  the  expense  of  the  starch  ingested 
(see  p.  290).  On  the  third  day  of  the  diet  the  protein  metab- 
olism had  fallen  to  one-third  that  observed  in  fasting  (see  p. 
280). 

The  sparing  influence  of  carbohydrate  oxidation  upon 
protein  metabolism  has  been  beautifully  illustrated  by  Lander- 
gren.4    Diets  containing  carbohydrates  and  fats,  but  scarcely 

1  Landergren:   "Skan.  Archiv  fur  Physiologie,"  1903,  xiv,  112. 

2  Folin:   "American  Journal  of  Physiology,"  1905,  xiii,  45. 

3  Cathcart:   ''Biochemische  Zeitschrift,"  1907,  vi,  109. 

4  Landergren:  Loc.  tit., 

18 


274  SCIENCE    OF   NUTRITION 

any  nitrogen  (about  one  gram  daily),  were  given  men  and  the 
protein  metabolism  noted.  This  condition  is  called  that  of 
specific  nitrogen  hunger.  After  four  days'  administration  of 
such  a  diet  the  urinary  nitrogen  may  be  reduced  to  less  than 
4  grams. 

In  one  experiment  in  which  this  was  accomplished  carbohy- 
drates were  entirely  replaced  by  fat,  with  the  result  that  pro- 
tein metabolism  rose  to  the  amount  found  in  starvation  (about 
10  grams).  It  has  already  (p.  248)  been  explained  that  inges- 
tion of  fat  alone  will  not  reduce  protein  metabolism  below 
that  of  starvation.     The  experiment  is  as  follows: 

Carbohydrate  Period.  Fat  Period. 

Diet  =  45.2  Cal.  per  Kg.  Diet  =  43.7  Cal.  per  Kg. 

N  in  Urine.  N  in  Urine. 

Day  o.  .  .'. 12.76*  Day  5 4.28 

"      1 "      6 8.86 

"      2 "      7 9.64 


3 

4 3-/6 


*  Ordinary  diet. 

On  day  5,  the  first  of  the  fat  diet,  it  is  evident  that  the  pro- 
tein metabolism  was  affected  by  the  use  of  the  glycogen  supply 
of  the  body,  an  influence  which  became  negligible  on  the  second 
and  third  days  of  the  fat  diet  (p.  72). 

Landergren  gives  the  following  results  in  various  cases  of 
specific  nitrogen  hunger,  showing  the  nitrogen  in  the  urine 
before  the  diet  and  after  four  days  thereof: 

11. 

N  in  urine  (ordinary  diet) 12.76 

N  in  urine  (specific  N  hunger).     3.76 
Calories  in  diet  per  kg 45.2 

This  reduction  of  protein  metabolism  to  4  grams  on  the 
fourth  day  was  brought  about  by  the  following  diets  in  the 
different  cases: 

II.     750  g.  carbohydrates =   45.2  cal.  per  kg. 

III.     300  g.  carbohydrates  4-  150  g.  fat.  ...    =   37.8    "         " 
V.     380  g.  carbohydrates  -j-  150  g.  fat.  ...    =   38.4    "        " 


III. 

IV. 

V. 

11.87 

3-95 
37-8 

13-7 
3-°4 
45 -o 

15-2 

4.2 
38.4 

INFLUENCE   OF   THE   INGESTION   OF   CARBOHYDRATE      275 


A  diet  containing  half  its  calories  in  carbohydrates  and  half 
in  fat  has  therefore  the  same  protein  protecting  power  as  one 
made  up  of  carbohydrates  alone.  This  demonstrates  the 
rationality  of  a  mixture  of  the  non-nitrogenous  food-stuffs. 

The  experiments  of  Karl  Thomas  have  shown  the  pro- 
longed influence  of  a  previous  high  protein  diet  upon  the 
nitrogen  output  in  the  urine  of  man.  A  starch-cream  diet  had 
reduced  the  urinary  nitrogen  elimination  to  2.2  grams  daily. 
Then,  during  four  days,  76,  87,  85,  and  71  grams  of  nitrogen 
were  given  in  the  diet.  The  nitrogen  retention  in  the  body 
for  the  first  four  days  was  +43,  +25,  +8,  and  —10  grams, 
a  total  of  +66  grams.  This  stored  protein  was  by  no  means 
as  rapidly  demolished  in  the  body  as  it  was  added  to  it.  This 
appears  in  the  third  column  of  the  following  table: 

THE  INFLUENCE  OF  PREVIOUS  PROTEIN  INGESTION  UPON  THE 
EXCRETION  OF  NITROGEN  IN  GRAMS  IN  MAN  WHEN  A  DIET 
OF   FAT  AND   CARBOHYDRATE   IS   ADMINISTERED. 


Last  normal  day 

(1 
3 
5 

I    6 

I    7 

Uq 

Meat  (2.9  gm.  N) 20 


Landergren.1 

KlNBERC.2 

Thomas.3 

12.8 

25-2 

77-7 

8.9 

18.3 

28.3 

5-2 

14-5 

10.7 

4-3 

11. 6 

5-i 

3-8 

9.1 

5-2 

8.0 

4-7 

7-3 

4.2 

5-6 

3-0 
2.2 

2.2 

Rubner4  has  defined  the  minimal  protein  metabolism 
under  conditions  of  administration  of  carbohydrate  in  excess, 
as  the  "wear-and-tear"  quota  of  protein  metabolism.  This 
minimal  level  is  only  achieved  after  the  reduction  of  the  cells 
from  their  optimal  protein  condition  through  loss  of  body 
nitrogen.     Rubner  estimates  that  a  kilogram  of  body  weight 

landergren:   Loc.  cit. 

2  Kinberg:    "Skan.  Archiv  f.  Physiologie,"  191 1,  xxv,  291. 

3  Thomas:    "Archiv  f.  Physiologie,"  1910,  Suppl.,  p.  249. 

4  Rubner:    "Archiv  fur  Hygiene,"  1908,  lxvi,  45. 


276  SCIENCE   OF   NUTRITION 

contains  30  grams  of  nitrogen.  Since  the  individual  investi- 
gated by  Thomas  weighed  73  kilograms,  he  contained  2190 
grams  of  nitrogen.  When  given  89  grams  of  protein  nitrogen 
on  a  single  day  this  represented  4.5  per  cent,  of  his  body's 
supply.  The  66  grams  of  protein  nitrogen  stored  during  the 
days  of  liberal  protein  ingestion,  which  raised  the  cells  to  an 
optimal  condition,  represented  3  per  cent,  of  the  total  protein 
content.  When  carbohydrates  alone  were  given  this  stored 
protein  was  only  gradually  eliminated — there  was  a  transition 
period  of  constantly  diminishing  protein  waste  until  a  minimum 
of  2.2  grams  of  urinary  nitrogen  (with  0.6  grams  in  the  feces) 
was  found.  The  urinary  nitrogen  then  represented  approx- 
imately 1  part  in  1000  of  protein  contained  in  the  organism. 
This  is  the  lowest  "wear-and-tear"  quota  of  protein  metabolism. 

It  is  a  point  of  debate  whether  the  "stored  protein"  becomes 
true  living  tissue  protein  or  whether  it  represents  a  special 
variety  of  deposit  protein,  which  is  retained  in  the  tissue  cells 
very  much  as  glycogen  is  retained  by  them  (seep.  81).  The 
storage  takes  place  largely  in  the  liver.1  It  would  be  interest- 
ing to  follow  the  sulphur  excretion  during  the  early  days  of 
the  transition  period  from  high  to  low  protein  metabolism  and 
note  whether  this  sulphur  elimination  runs  parallel  to  that 
of  nitrogen  in  the  usual  ratio  (see  p.  169).  Should  this  be 
the  case  it  would  indicate  that  "deposit  protein"  was  the  same 
as  tissue  protein.  Phosphorus  retention  is  not  always  pres- 
ent during  the  period  of  protein  deposit  (see  p.  287). 

Rubner  has  given  further  useful  definitions.  A  "repair 
quota"  of  protein  is  required  in  the  food  in  order  to  replace 
that  lost  in  the  "wear  and-tear"  quota.  A  "growth  quota" 
of  protein  is  necessary  in  addition  to  a  repair  quota  under  the 
circumstances  of  multiplication  of  cells  and  of  developing 
protoplasm  in  the  young.  Furthermore,  an  "improvement 
quota"  of  protein  may  be  necessary  in  the  adult  after  wasting 
disease,  or  after  fasting,  in  order  to  bring  the  cells  to  an  opti- 

1  Tichmeneff:  "Biochemische  Zeitschrift,"  1914,  lix,  326,-  Cahn-Bronner: 
Ibid.,  1914,  lxvi,  289. 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   277 

mum  of  protein  condition,  thereby  improving  the  welfare  of 
the  living  organized  protein.1  When  protein  is  given  in  excess 
so  that  it  is  not  used  for  repair  nor  for  growth  nor  deposit, 
its  constituent  amino-acids  are  deaminized  and  the  residual 
oxy-  or  keto-acids  are  in  part  converted  into  glucose,  in  part 
into  fatty  acid,  thus  yielding  fuel  to  the  cells  just  as  would 
carbohydrate  and  fat.  This  fraction  of  protein  Rubner 
designates  as  the  "dynamic  quota." 

Thomas  calculated  that  during  the  period  of  minimal 
"wear-and-tear"  protein  metabolism,  0.4  calories  were  de- 
rived from  the  metabolism  of  1.5  milligrams  of  protein  per 
kilogram  of  body  weight  every  hour,  while  0.96  calories  were 
derived  from  the  oxidation  of  259  milligrams  of  glucose.  In 
other  words,  protein  furnished  only  4  per  cent,  of  the  energy 
required  by  a  man  at  rest.  Since  mechanical  work  scarcely 
influences  the  "wear-and-tear"  quota  of  protein  metabolism 
(see  p.  311),  although  it  largely  increases  the  oxidation  of 
carbohydrate,  it  is  evident  that  protein  may  play  a  very  small 
role  as  a  producer  of  energy  for  the  maintenance  of  the 
function  of  life. 

When  carbohydrates  are  given  in  the  diet,  it  is  possible 
to  establish  nitrogen  equilibrium  at  a  much  lower  level  than 
when  protein  alone  or  protein  and  fat  are  ingested. 

When  carbohydrates  and  protein  are  ingested  together  in 
quantity  sufficient  for  the  requirement  of  the  organism,  it  has 
been  found  that,  taking  the  starvation  protein  metabolism  as 
one,  nitrogen  equilibrium  can  be  maintained  by  ingesting  one 
part  of  protein.2 

The  work  of  Siven,3  however,  was  the  first  indication  that 
nitrogen  equilibrium  may  be  maintained  at  even  a  lower  level 
than  that  ordinarily  present  in  starvation.  A  somewhat 
undersized  healthy  man,  weighing  60  kilograms,  who  normally 
ate  a  mixed  diet  containing  16  grams  of  nitrogen,  was  given 
less  and  less  protein,  and  an  attempt  was  made  to  establish 

1  Rubner:    "Archiv  fur  Physiologie,"  191 1,  p.  67. 

2  E.  Voit  and  Korkunoff:    "Zeitschrift  fur  Biologie,"  1895,  xxxii,  117. 

3  Siven:   "Skan.  Archiv  fur  Physiologie,"  1900,  x,  91. 


278 


SCIENCE   OF   NUTRITION 


nitrogen  equilibrium  at  lower  and  lower  levels.     The  daily 
ration  was  rich  in  carbohydrates  and  yielded  2444  calories. 
The  experiment  was  divided  into  four  periods  of  about  a 
week  each,  which  may  be  summarized  as  follows: 


Length  in  Days. 

N  IN  THE 

Food. 

Days  Until  N 

Equilibrium 

was  Obtained. 

N  Loss  Before  ,t          n  ^ 
N  Equilibrium  ■    °       B 
was  Obtained. 

1,7 

II,  8 

12.69 

10.40 

8.71 

6.26 

1 

1 

at  once 

3 

0-53 
°-34 

2.09 

+9-73 
+6.04 

111,6. 

IV,  6 

+4-39 
-0.58 

It  is  apparent  that  nitrogen  equilibrium  may  be  established 
after  ingesting  6.26  grams  of  nitrogen,  although,  as  has  been 
seen,  the  elimination  during  the  early  days  of  starvation  in  man 
is  usually  10  grams.  During  the  first  three  periods  of  reduced 
protein  intake,  as  much  as  20.16  grams  of  protein  nitrogen 
were  actually  added  to  the  body.  In  a  fifth  period  nitrogen 
equilibrium  was  obtained  on  the  fourth  day  on  a  diet  contain- 
ing 4.52  grams  of  nitrogen. 

Thomas1  administered  during  frequent  intervals  small 
quantities  of  meat  washed  free  from  extractives  to  the  man 
who  had  partaken  of  a  starch-cream  diet  and  had  reduced  his 
protein  metabolism  to  one  represented  by  a  minimum  of  2.2 
grams  of  urinary  nitrogen  daily.  Nitrogen  equilibrium  was 
nearly  achieved  after  administration  of  that  quantity  of 
protein  nitrogen  which  corresponded  to  the  quantity  eliminated 
in  the  urine  and  feces.     This  is  shown  below  in  grams  per  day: 

Day.  49  50  51  52  S3  S4  55 

N  in  diet o  o  2.S9  2.89  2.61  2.61  o 

N  in  urine 2.31  2.16  2.23  2.48  2.56  3.13  3.49 

N  in  feces 0.74  0.73  0.74  0.73  0.74  0.73  0.74 

N  loss —  3.05  —2.89  —0.08  —0.32  —0.69  —1.25  —4.23 


In  this  experiment  the  ingestion  of  the  quantity  of  protein 
which  was  the  equivalent  of  the  "wear-and-tear"  quota  was 

'Thomas:   "Archiv  fur  Physiologie,"  1910,  Suppl.,  p.  249. 


INFLUENCE    OF   THE   INGESTION   OF    CARBOHYDRATE      279 

at  first  nearly  sufficient  to  completely  "repair"  the  tissue. 
While  living  upon  this  low  protein  diet  the  mental  and  mus- 
cular power  was  unchanged. 

Chittenden1  finds  that  nitrogen  equilibrium  may  be  main- 
tained on  a  diet  containing  a  very  small  amount  of  protein  and 
two-thirds  of  the  body's  requirement  of  energy.  The  first 
experiment  was  on  Fletcher  and  lasted  six  days.  The  daily 
ration  contained  7.19  g.  nitrogen  +  38.0  g.  fat  -f  253  g.  car- 
bohydrates =  21.3  calories  per  kilogram.  The  excreta  con- 
tained 6.90  grams  of  nitrogen  daily.  On  this  diet  the  indi- 
vidual showed  "remarkable  physical  strength  and  endurance." 

Another  experiment  was  performed  by  Chittenden  on  him- 
self and  lends  itself  for  interesting  comparison  with  the  results 
of  the  ingestion  of  a  maintenance  ration.  The  food  was 
principally  vegetable.     The  results  may  be  thus  tabulated: 

A  LOW  LEVEL  OF  NITROGEN  EQUILIBRIUM  IN  NORMAL  AND 
UNDERNUTRITION 


Date. 

Die 
N  in  Grams. 

T. 

Cal.  per  Kg. 

N  Excretion. 

N  Balance. 

March  23 

March  25 

6.70 
6.8S       . 

34-7 
22.4 

6.56 
6-34 

+0.23 
+0-54 

Nitrogen  equilibrium  may  therefore  be  maintained  at  a  low 
level,  even  during  the  state  of  undernutrition  present  when 
22.4  calories  per  kilogram  are  in  the  daily  diet.  On  a  milk  diet 
Rubner2  found  that  the  ingestion  of  2483  grams  of  milk  con- 
taining 84  grams  of  protein  and  two-thirds  the  body's  require- 
ment of  energy  resulted  in  the  addition  of  6.7  grams  of  protein 
to  the  body  daily  for  three  days  (see  p.  353). 

It  is  a  valuable  piece  of  information  to  know  that  one  may 
diet  an  obese  patient  on  a  food  containing  little  protein  and 
two-thirds  the  body's  energy  requirement  without  danger  of 


1  Chittenden:   "Physiological  Economy  in  Nutrition, 

2  Rubner:   "Zeitschrift  fur  Biologie."  1879,  xv,  130. 


1904,  pp.  14,  40. 


28o 


SCIENCE   OF   NUTRITION 


protein  loss.  The  other  third  of  the  necessary  energy  will  be 
furnished  by  the  body's  own  store  of  fat.  It  is  not  remarkable 
that  the  body  is  capable  of  great  physical  effort  on  such  a  diet, 
for  a  fasting  man  is  also  competent  in  this  direction  (see  p.  71). 
In  Chapter  on  p.  156  mention  was  made  of  the  sparing  action 
of  gelatin  on  protein  metabolism,  and  its  ingestion  was  found  to 
prevent  about  23  to  37.5  per  cent,  of  the  protein  loss  during 
starvation.  Murlin1  in  an  extensive  series  of  experiments  has 
shown  that  the  sparing  power  of  gelatin  is  greater  than  this 
when  it  is  ingested  with  a  mixed  diet.  He  finds  that  if  the 
quantity  of  nitrogen  eliminated  in  fasting  be  taken  as  one, 
then  nitrogen  equilibrium  may  be  maintained  in  dogs  and  in 
man  on  ingestion  of  a  diet  rich  in  carbohydrates,  whether  the 
nitrogen  of  the  diet  be  protein  nitrogen  equal  to  one  or  whether 
it  contain  one-third  protein  plus  two-thirds  gelatin  nitrogen. 
This  is  shown  in  the  following  experiment  on  a  man,  the  results 
being  expressed  in  averages  per  day: 

EFFECT    OF    ADMINISTERING     GELATIN     IN    A    MIXED    DIFT 

IN  MAN 

N  elimination  on  a  third  day  of  fasting  =  13.23  gm. 


Source  of  N  in  Diet. 


All  protein  N 

Two-thirds  (63%)  gelatinl 
N  -f-  one-third  protein  Nj  ' 
All  protein  N 


No. 

OF 

Days. 


Cal. 

in 

Food. 


3208 
3620 
3220 


Cal. 

PER 

Kg. 


47 
46 


N  IN 

Food. 


Grams. 

14-25 

14-53 
14.26 


N  in  Ex- 
creta. 


Grams. 
*3-33 
13-82 
13-52 


N  TO 

Body. 


Grams. 
+0.87 

+0.71 

+0.74 


Murlin2  also  showed  that  the  sparing  power  of  gelatin  was 
due  to  its  immediate  chemical  nature,  and  not  to  the  60  per 
cent,  of  glucose  which  can  arise  from  it  in  metabolism  (see 
p.  174).  For  example,  a  fasting  dog  was  given  12  grams  of 
glucose  daily  for  four  days  after  thirteen  days  of  fasting;  then 
20  grams  of  gelatin  were  substituted  during  a  period  of  four 
days.     The  glucose  scarcely  exerted  any  sparing  power  over 

1  Murlin:    "American  Journal  of  Physiology,"  1907,  xix,  285. 

2  Murlin:  Ibid.,  1907,  xx,  234. 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   28 1 


the   protein   metabolism,   whereas   the   ingestion   of   gelatin 
showed  the  usual  sparing  of  31  per  cent. 

The  same  fact  was  demonstrated  on  a  man  who  was  brought 
into  nitrogen  equilibrium  on  an  adequate  mixed  diet  containing 
10  grams  of  nitrogen  and  carbohydrates  enough  to  supply  50 
per  cent,  of  the  energy.  The  state  of  nitrogen  equilibrium  was 
not  quite  maintained  when  gelatin  was  used  as  the  source  of 
two-thirds  of  the  nitrogen  in  the  diet.  Murlin  explained  this 
as  being  due  to  a  dislike  for  sweets  on  the  part  of  the  indi- 
vidual so  that  he  could  not  take  carbohydrates  in  large  excess. 
However,  when  the  nitrogen  of  the  diet  was  reduced  so  as  to 
contain  only  protein  nitrogen  equal  to  one-third  that  elimin- 
ated in  fasting,  together  with  the  60  per  cent,  of  glucose 
which  could  have  originated  from  the  gelatin  previously 
ingested,  the  waste  of  body  nitrogen  rose  far  above  that 
observed  when  gelatin  and  other  protein  were  given.  The 
experiment  may  thus  be  presented: 

INFLUENCE  OF   GELATIN  IN  METABOLISM 

Figures  are  for  the  last  day  of  each  period 


Source  of  N  in  Diet. 

No. 

OF 

Days. 

Cal. 

IN 

Food. 

Cal. 

PER 

Kg. 

NlN 

Food. 

N  in  Ex- 
creta. 

N  to 
Body. 

Meat  +  veg.  protein  N*. 
Two-thirds  (67C7C)  gelatin     1 
N+one-third  veg.  protein  Nj 
One-third  veg.  protein  N.  .  . 

4 
6 

3 

1971 

1935 
1858 

43 
42 
40 

Grams. 
10.05 

9.62 
3-23 

Grams. 
10.35 
IO.I2 

5-62 

Grams. 
-0.30 

-0.50 
-2-39 

*  Two-thirds  meat  N  +  one-third  vegetable  N  in  wheat,  oats,  and  rice. 


Here  the  rise  in  the  metabolism  of  body  protein  corresponds 
to  the  withdrawal  of  gelatin  from  the  diet  even  in  the  presence 
of  a  considerable  intake  of  carbohydrate.  Hence  Landergren's1 
interpretation  that  the  rise  in  nitrogen  elimination,  which 
takes  place  on  changing  from  a  pure  carbohydrate  to  a  pure 
fat  diet,  is  due  to  the  body's  absolute  requirement  for  carbohy- 


P-  68  = 


'Landergren:  Inaugural  Dissertation,  1902:  "Maly's  Jahresbericht,"  1902, 


282  SCIENCE   OF   NUTRITION 

drate  and  that  it  obtains  this  by  increasing  its  protein  metab- 
olism is  scarcely  tenable,  although  even  now  this  point  is 
emphasized  by  many  writers. 

It  is  evident  that  the  "wear-and-tear"  quota  of  protein 
metabolism  must  be  covered  by  the  ingestion  of  an  equal 
"repair"  quota,  while  the  additional  "dynamic"  quota  may 
be  supplied  by  protein  or  by  gelatin.  Murlin  found  that 
the  "repair"  quota  was  best  administered  in  the  form  of 
beef  heart,  and  that  the  proteins  of  biscuit  meal  were  very 
inefficient  as  sparers  of  body  protein. 

In  the  course  of  his  experiments  Murlin  found  that  the 
longer  the  animal  had  fasted,  that  is,  the  lower  its  protein 
condition,  the  more  readily  did  gelatin  reduce  the  waste  of 
body  protein. 

Murlin  also  showed  that  three-quarters  of  the  starvation 
nitrogen  ingested  as  gelatin  and  one-quarter  as  protein  were 
not  able  to  maintain  nitrogen  equilibrium  in  the  dog.  Two- 
thirds  the  starvation  nitrogen  requirement  ingested  as  gelatin 
and  one-third  as  protein  maintain  nitrogenous  equilibrium. 
Carbohydrates  ingested  alone  reduce  protein  metabolism  to 
one- third  that  found  in  starvation.  One-third  the  starvation- 
quantity  seems  to  be  the  lower  limit  of  protein  metabolism 
compatible  with  life. 

It  may  also  be  noted  that  in  a  fasting  diabetic  dog  the 
protein  metabolism  may  rise  to  fivefold  that  noted  in  simple 
fasting  (see  p.  463),  or  fifteenfold  the  irreducible  minimum  of 
the  "wear-and-tear"  quota.  Under  these  circumstances  the 
writer  has  found  that  pure  gelatin  given  alone  is  more  effective 
as  a  protein  sparer  than  it  is  in  simple  fasting.  Thus  after 
giving  30  grams  of  gelatin  to  a  fasting  phlorhizinized  dog  the 
following  results  were  obtained  on  analyzing  the  urine  every 
twelve  hours: 

Glucose.  N.  Body  N. 

Fasting,  twelve  hours 1 2.58  3.77  — 3-77 

Gelatin  (=  4.644  g.  N),l  <-.-  £ 

\      t    tt  &       /ji 20.00  6.02  —1-37 

twelve  hours  j  ° 

Fasting,  twelve  hours 3.79  —  3.79 


INFLUENCE    OF   THE   INGESTION   OF  CARBOHYDRATE      283 

If  the  fecal  nitrogen,  which  is  very  small  after  gelatin 
ingestion,  be  neglected,  it  may  be  calculated  that  body  protein 
was  spared  to  the  extent  of  63.7  per  cent,  after  the  administra- 
tion of  gelatin  instead  of  30  per  cent,  as  in  ordinary  fasting. 
One  may,  therefore,  conclude  that  the  great  waste  of  body 
protein  which  takes  place  in  diabetes  belongs  in  Rubner's 
category  of  "dynamic"  protein  metabolism,  for  which  gelatin 
may  be  largely  used  as  a  substitute. 

McCollum1  gave  to  a  pig  a  diet  of  starch  and  salts  contain- 
ing 90  calories  per  kilogram  of  body  weight  for  twenty-four 
days  and  then  during  eight  days  added  gelatin,  the  nitrogen 
content  of  which  equalled  the  urinary  nitrogen  excretion  at 
the  end  of  the  starch  period.  The  results  showed  a  sparing 
of  the  minimal  endogenous  protein  metabolism  (the  "wear- 
and-tear"  quota)  equal  to  40  per  cent.,  as  appears  below: 


Starch  diet,  twenty-fourth) 
day 


N  in  Urine  Feces  Total  Loss  to 

Diet.  N.  N.                 N.  Body. 

o  2.59  0.04            3.53  -3.53 

Starof«tghg,eldt°'aVerageV-2^  3.73  ..04            4.76  -,,4 


The  creatinin  nitrogen,  which  remained  at  the  same  daily 
level  throughout  the  experiment,  was  at  the  start  18.3  per 
cent,  of  the  total  urinary  nitrogen.  It  is  interesting  to  note 
that  the  reduction  in  the  amount  of  endogenous  protein 
metabolism  brought  about  by  the  ingestion  of  gelatin  is 
exactly  the  same  quantity  which  may  be  withdrawn  from  the 
endogenous  metabolism  in  the  form  of  glycocoll  following  the 
ingestion  of  sodium  benzoate  (see  p.  188).  The  creatinin  excre- 
tion is  not  affected  in  either  case.  It  is  interesting  to  specu- 
late whether  the  exogenous  amino-acids  of  gelatin  replace  in 
metabolism  that  part  of  the  "wear-and-tear"  quota  which 
involves  the  endogenous  production  of  glycocoll. 

Curiously  enough,  the  endogenous  protein  metabolism 
may  be  greatly  reduced  when  ammonium  acetate  or  citrate  are 

1  McCollum:    "American  Journal  of  Physiology,"  1911-12,  xxix,  215. 


284  SCIENCE   OF   NUTRITION 

added  to  a  rich  carbohydrate  diet.  This  subject  was  first 
studied  by  Grafe,1  who  announced  that  nitrogen  equilibrium 
could  be  maintained  with  carbohydrate  and  ammonium  acetate 
in  the  diet,  and  who  saw  in  this  a  synthetic  formation  of  pro- 
tein within  the  organism.  Even  the  ingestion  of  ammonium 
chlorid  reduced  the  amount  of  protein  metabolism.  A  paper 
by  Abderrialden2  followed  quickly,  which  showed  that  though 
ammonium  acetate  when  given  with  starch,  sugar,  fat,  and 
bone-ash  greatly  reduced  the  endogenous  metabolism,  yet 
nitrogen  equilibrium  could  not  be  attained  under  these 
circumstances.  Abderhalden  believes  it  possible  that  the 
animal  cell  may  synthesize  alanin,  serin,  or  even  cy stein  under 
these  conditions,  although  he  thinks  that  the  heterocyclic 
and  aromatic  amino-acids  are  much  less  likely  to  be  formed. 
He  suggests  that  the  mass  action  of  ingested  ammonia  may 
prevent  the  deamination  of  some  of  the  amino-acids,  which 
may  therefore  be  used  once  again  for  the  repair  of  the  tissue. 
Abderhalden's  explanation  seems  the  more  rational  of  the 
two.  A  considerable  sparing  of  endogenous  protein  metab- 
olism was  observed  by  Grafe3  to  take  place  after  the  adminis- 
tration of  ammonium  citrate  with  carbohydrate,  and  this  has 
been  confirmed  by  Underhill,4  who,  however,  could  find  no 
influence  exerted  by  ammonium  chlorid. 

Grafe5  has  announced  that  urea  when  given  with  carbohy- 
drate protects  body  protein  from  waste  just  as  ammonium 
citrate  does.  This  is  denied  by  Abderhalden.6  Henriques 
and  Andersen7  explain  Grafe's  results  as  due  to  the  growth  of 
bacteria  within  the  medium  of  the  intestinal  tract  of  herbivora. 


1  Grafe  and  Schlapfer:    "Zeitschrift  fur  physiologische  Chemie,"   191 2, 
lxxvii,  1. 

2  Abderhalden:  Ibid.,  1912,  lxxviii,  1.    A  vast  literature,  experimental  and 
polemical,  has  arisen  from  these  two  papers. 

3  Grafe:    "Zeitschrift  fur  physiologische  Chemie,"  191 2,  lxxxii,  347. 

4  Underhill  and  Goldschmidt:     "Journal  of  Biological  Chemistry,"  1913, 
xv,  341. 

5  Grafe  and  Turban:   "Zeitschrift  fur  physiologische  Chemie,"  1913,  lxxxiii, 

25- 

6  Abderhalden:  Ibid.,  1913,  lxxxiv,  218. 

7  Henriques  and  Andersen:  Ibid.,  1914,  xcii,  21. 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   285 

Rats  may  be  maintained  when  given  such  bacterial  masses  as 
the  source  of  their  protein  food. 

Lower  organisms  have  the  power  to  synthesize  protein 
from  sugar  and  some  simple  source  of  nitrogen.  Thus, 
Armand-Delille1  found  that  the  tubercle  bacillus  grew  as  well 
in  a  culture-medium  of  sugar,  glycerin,  glycocoll,  and  arginin, 
with  addition  of  appropriate  salts,  as  it  did  in  a  solution  of 
1  per  cent,  of  peptone  in  bouillon. 

Delbriick,  in  Germany,  discovered  that  yeast  cells  devel- 
oped rapidly  and  formed  body  protein  when  they  were  placed 
in  a  solution  of  sugar  and  ammonium  sulphate.  The  mass 
thus  developed  is  stated  to  have  been  used  on  a  large  scale  as 
a  source  of  protein  food  for  cattle  during  the  time  of  fodder 
scarcity  introduced  by  the  present  war. 

Lower  organisms  may  therefore  form  the  various  aliphatic, 
aromatic,  and  heterocyclic  amino-acids  from  carbohydrate 
and  ammonium  salts. 

Within  the  body  of  the  mammal  there  is  evidence  that 
some  of  the  simpler  deamination  reactions  are  reversible 
(see  p.  194),  but  the  experiments  with  gelatin  demonstrate 
that  when  tryptophan  and  phenylalanin  are  lacking  these 
important  building-stones  of  protein  cannot  be  synthesized, 
for  nitrogen  equilibrium  can  only  be  obtained  when  they  are 
admixed  with  the  gelatin  food.  The  consideration  of  other 
"deficient"  proteins  will  be  given  elsewhere. 

The  cause  of  the  great  reduction  in  the  fasting  quantity 
of  protein  metabolism  when  carbohydrates  alone  are  ingested 
has  been  thus  stated  by  Knoop:2  "The  animal  body  may 
therefore  synthesize  amino-acids  from  ammonia.  If  amino- 
acids  can  be  produced  from  oxyacids,  such  as  originate  from 
carbohydrate  metabolism,  for  example,  then  it  is  possible  to 
comprehend  chemically  not  only  the  production  of  sugar  from 
protein  but  also  reactions  in  a  reverse  direction.  The  minimal 
nitrogen  metabolism  of  fasting  may  be  reduced  either  through 

1  Armand-Delille,  Mayer,  Schaeffer,  and  Terroine:  "Archive  de  Physiologie 
et  de  Pathologie  generale,"  1913,  xv,  797. 

2  Knoop:    "Zeitschrift  fiir  physiologische  Chemie,"  1910,  Lxvii,  489. 


286  SCIENCE   OF   NUTRITION 

the  ingestion  or  through  the  intermediary  production  of  non- 
nitrogenous  acids,  which  unite  with  ammonia  prior  to  its 
synthesis  to  urea  and  form  amino-acids." 

Since  amino-acids  when  ingested  tend  to  reduce  protein 
metabolism  this  seems  a  plausible  hypothesis.  However,  one 
should  bear  in  mind  the  experiment  of  McCollum  (see  p.  188), 
in  which  40  per  cent,  of  the  urinary  endogenous  protein  nitro- 
gen could  be  removed  in  the  form  of  glycocoll  when  benzoate 
of  soda  was  ingested  without  affecting  the  amount  of  protein 
metabolism.  This  glycocoll  nitrogen  when  once  bound  as 
hippuric  acid  could  not  have  participated  in  any  interplay  of 
chemical  reaction  with  keto-  or  oxyacids  produced  in  carbohy- 
drate metabolism. 

Rubner  has  called  attention  to  the  extremely  soluble 
character  of  the  monosaccharids,  and  it  may  be  that  a  plethora 
of  carbohydrate  molecules  reduces  the  demands  upon  the 
structural  protein  of  the  cells.  Furthermore,  it  has  been 
noted  that  the  production  of  /3-oxybutyric  acid  is  associated 
with  an  increased  protein  breakdown  (see  p.  94),  so  that  the 
action  of  carbohydrate  may  perhaps  prevent  chemical  injury 
to  the  cellular  framework  by  promoting  the  normal  oxidation 
of  /?-oxybutyric  acid. 

Since  carbohydrates  so  effectively  spare  protein  from  com- 
bustion, it  would  seem  logical  that  their  use  should  render  the 
retention  of  ptotein  in  the  body  easier  than  when  fat  is  given 
with  protein. 

Liithje1  finds  a  long-continued  nitrogen  retention  in  man 
when  much  nitrogen  in  protein  is  ingested  (up  to  50  gm.  N 
daily!)  and  carbohydrates  and  fat  making  a  total  of  4000 
calories  or  66  calories  per  kilo.  (See  also  Bornstein's  experi- 
ment, p.  154.) 

In  a  subsequent  paper  Liithje2  finds  that  the  P205  retention 
in  convalescence  is  that  which  corresponds  to  the  retention  of 
protein   for    the   formation   of  new   tissue,  including  bone. 

1  Liithje:   "Zeitschrift  fur  klinische  Medizin,"  1902,  xliv,  22. 

2  Liithje:    "Deutsches  Archiv  fiir  klinische  Medizin,"  1904,  lxxxi,  278. 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   287 

Sometimes  in  a  healthy  person  not  enough  P205  is  retained  to 
build  up  "flesh,"  and  the  protein  retained  must,  therefore,  exist 
in  the  form  of  "deposit  protein."  This  protein,  he  says,  is 
not  stored  in  the  blood,  for  the  composition  of  the  blood  does 
not  alter,  but  is  perhaps  retained  in  the  cellular  fluids,  just  as 
glycogen  is  retained  by  the  cells. 

Rubner  states  that  the  greater  the  impoverishment  of  the 
protein  supply  in  an  animal  fed  with  fat,  the  more  powerful  is 
the  protective  effect  of  small  quantities  of  ingested  protein  over 
the  loss  of  body  protein.  Also  the  retention  of  protein  de- 
pends on  the  protein  content  of  the  animal  as  well  as  on  the 
quantity  of  protein  ingested.  This  is  illustrated  in  the  follow- 
ing table: 

INFLUENCE  OF  THE  PROTEIN  CONTENT  OF  A  DOG  ON  THE 
RETENTION  OF  PROTEIN  INGESTED 

Total  N  Content  N  in  Terms  of  100  N  in  Dog 

of  Dog.  in  Food.  to  Body. 

318.8 5-25  +1-65 

354-7 5-57  +1.02 

310.6 6.72  +2.64 

363-7 I2-79  +2-62 

It  is  evident  from  this  that  of  the  same  diet  of  protein  more 
will  be  retained  when  the  nitrogen  content  of  the  dog  is  low 
than  when  it  is  high ;  and  also  that  a  small  protein  intake  may 
cause  the  same  retention  of  nitrogen  as  a  large  protein  intake, 
if  in  the  first  instance  there  be  a  relative  impoverishment  of  the 
protein  content  of  the  animal. 

According  to  these  laws  adult  cells  which  have  been  de- 
pleted of  their  protein  may  gradually  improve  their  nutritive 
condition  until  they  reach  an  optimum,  at  which  point  they 
lose  their  power  to  attach  additional  protein. 

This  is  also  illustrated  in  an  experiment  by  McCollum,1 
who  gave  to  a  pig  a  diet  containing  14  grams  of  nitrogen  per 
day  in  the  form  of  casein  and  starch,  so  that  the  value  of  the 
diet  was  100  calories  per  kilogram  during  a  period  of  thirty-six 
days.     The  animal  retained  43  per  cent,  of  the  nitrogen  in- 

1  McCollum:    "American  Journal  of  Physiology,"  1911-12,  xxix,  215. 


288  SCIENCE   OF   NUTRITION 

gested.  During  the  first  three  days  it  added  9.65  grams  of 
nitrogen  to  the  body  daily;  during  the  last  three,  3.69  grams. 
With  the  increase  in  active  protoplasm  the  creatinin  nitrogen 
excretion  rose  from  0.24  to  0.31  grams  per  day. 

The  conditions  of  protein  metabolism  are  entirely  similar 
to  those  of  starch  metabolism:  (1)  Digestive  hydrolysis;  (2) 
partial  combustion  of  the  end-products;  and  (3)  possible 
regeneration  of  portions  of  the  end-products  into  substances 
akin  to  the  originals  but  characteristic  of  the  organism — i.  e., 
glycogen  and  body  proteins.  In  the  case  of  proteins  the 
second  or  metabolic  process  involves  the  production  of  sugar 
and  of  fatty  acids  from  the  amino-acids  involved.  The  third 
or  regenerative  process  is  promoted  by  such  a  protein  as  casein, 
which  yields  the  proper  variety  of  cleavage  products. 

In  conclusion,  it  may  be  said  that  carbohydrates  are  the 
most  economical  of  the  food-stuffs,  both  physiologically  and 
financially.  They  are  the  greatest  sparers  of  protein.  In- 
gestion of  fat  has  for  its  object  the  relieving  of  the  intestine 
from  excessive  carbohydrate  digestion  and  absorption.  Inges- 
tion of  fat  in  too  large  quantities  leads  to  digestive  distur- 
bances, and  if  carbohydrates  are  entirely  abandoned,  to 
acetonuria. 


CHAPTER  X 

THE    INFLUENCE   OF   THE   INGESTION  OF  CARBO- 
HYDRATE 

PART  II— THE   RESPIRATORY  METABOLISM 

In  a  previous  chapter  (see  p.  238)  it  has  been  stated  that 
when  Rubner  gave  cane-sugar  to  a  dog  and  measured  the 
metabolism  during  a  period  of  twenty-four  hours  the  heat 
production  was  raised  by  an  increment  amounting  to  about 
5  per  cent,  of  the  calories  ingested.  This  fact,  which  has  been 
repeatedly  confirmed,  does  not  tell  the  whole  story,  because 
the  absorption  of  the  very  soluble  sugar  takes  place  in  the  first 
few  hours.  Thus  Magnus-Levy1  noticed  that  after  giving  155 
grams  of  cane-sugar  to  a  man  there  was  a  maximal  increase 
in  metabolism  of  12  per  cent.,  with  a  return  to  the  basal  level 
during  the  fifth  hour  after  taking  the  food-stuff. 

Johansson,  Billstrom,  and  Heijl2  have  shown  that  if  50  to 
200  grams  of  cane-sugar  be  given  a  fasting  man,  the  carbon 
dioxid  output  increases  from  22.6  grams  per  hour  to  about  30 
grams  per  hour.  The  larger  ingestion  did  not  produce  a 
higher  elimination  of  carbon  dioxid  than  does  the  smaller 
amount.  This  indicates  the  evenness  with  which  sugar 
entering  the  blood-stream  is  utilized  by  the  organism.  If 
sugar  be  present  in  excess  it  may  be  stored  as  glycogen  until  it 
is  needed  by  the  cells.  The  rise  in  the  carbon  dioxid  output 
was  greater  after  fructose  is  ingested  than  after  glucose  is  given. 
This  was  explained  as  due  to  the  fact  that  fructose  is  less  readily 

1  Magnus-Levy:   "Pfltiger's  Archiv,"  1894,  Iv,  1. 

2  Johansson,  Billstrom,  and  Heijl:  "Skan.  Archiv  fur  Physiologie,"  1904, 
xvi,  263. 

19  289 


290 


SCIENCE   OF   NUTRITION 


retained  in  the  liver  as  glycogen,  and  therefore  reaches  the 
tissues  in  a  larger  stream  than  does  glucose  under  similar 
circumstances,  and  hence  more  completely  replaces  fat  as  the 
source  of  energy.  In  a  later  paper  Johansson1  explains  that 
after  ingesting  200  grams  of  glucose  containing  740  calories, 
or  one-quarter  the  man's  energy  requirement  for  a  day,  the 
rise  in  carbon  dioxid  output  lasts  for  six  hours  and  then  falls  to 
the  fasting  basis.  This  is  an  indication  of  the  ready  absorption 
and  combustion  of  ingested  glucose.  If  there  has  been  pro- 
longed fasting,  ingested  glucose  may  cause  no  rise  in  the  car- 
bon dioxid  output  in  man  on  account  of  its  conversion  into 
glycogen.     (See  p.  273.) 

Durig2  gave  100  grams  of  glucose  to  a  man  and  compared 
the  metabolism  with  that  obtained  after  giving  100  grams  of 
fructose.  In  the  latter  case  the  heat  production  as  measured 
by  indirect  calorimetry  was  10  per  cent,  greater  than  in  the 
former;  the  respiratory  quotients  were  usually  higher,  being 
more  frequently  over  unity,  and  therefore  indicating  a  readier 
conversion  of  fructose  into  fat  than  was  the  case  with  glucose. 

Du  Bois3  made  calorimetric  observations  on  men  after 
giving  100  and  200  grams  of  glucose  and  noted  the  following 
increases  above  the  basal  metabolism: 

PERCENTAGE  INCREASE  IN  HEAT  PRODUCTION  AFTER  GIVING 
GLUCOSE  TO   MAN 


HouRi  After  Food 

Subject  E.  F.  D.  B.,  100  grams 
glucose 

(R.Q-) 

Subject  E.  F.  D.  B.,  200  grams"! 
glucose  / 

(R.  Q-) 

Subject  L.   C.  M.,   200  grams\ 

glucose  / 

(R.Q.) 


I 

2 

3 

4 

3 

11 

0 

6 

{0.91) 

io.Sg) 

(0.88) 

(0.90) 

13 

17 

8 

(0.95) 

io.93) 

(0.95) 

24 

16 

16 

(0.92) 

(i.OO'l 

U-02) 

7 
(1. 00) 


1  Johansson:    ''Skan.  Archiv  fur  Physiologie,"  1908,  xxi,  30. 

2  Togel,  Brezina,  and  Durig:   "Biochemische  Zeitschrift,"  1013, 1,  298. 

3  Gephart  and  Du  Bois:    "Archives  of  Internal  MedicincJ  1915,  xv,  835. 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   29 1 


One  hundred  grams  of  glucose  caused  an  average  increase 
of  9  per  cent,  in  the  heat  production  and  200  grams  one  of 
12.5  per  cent,  during  three  to  six  hours  after  their  ingestion  by 
a  man  of  75  kilograms  in  weight.  Ingestion  of  200  grams  of 
glucose  by  a  man  of  60  kilograms  weight  caused  an  increase  of 
16  per  cent,  in  the  heat  production.  When  the  larger  quantity 
was  administered,  the  respiratory  quotients  indicated  that  the 
heat  production  was  entirely  at  the  expense  of  carbohydrate 
and  protein. 

The  behavior  of  carbohydrate  in  many  of  its  details  may 
be  best  observed  in  experiments  on  animals. 

Extensive  calorimetric  observations  upon  dogs  have  been 
carried  out  in  the  author's  laboratory,  and  the  following 
principles  are  believed  to  have  been  established: 

After  giving  50  grams  of  glucose  to  a  dog  Fisher  and 
Wishart1  found  an  increase  in  the  percentage  quantity  of  blood- 
sugar  at  the  end  of  the  first  hour,  and  this  was  followed  by  a 
fall  to  the  normal  level.  A  similar  phenomenon  had  been 
observed  in  man2  after  giving  150  grams  of  glucose;  but  in 
the  dog  it  was  further  observed  that  when  the  sugar  solution 
was  given  there  was  at  first  a  considerable  reduction  in  the 
quantity  of  urine  eliminated.  This  appears  from  the  following 
analysis : 

QUANTITY  OF  URINE  AS  INFLUENCED   BY  FASTING  AND   BY 
WATER  AND   GLUCOSE  INGESTION 


150  c.c. 

Water. 

Glucose  so  Gm. 

Glucose  7<;  Gm. 

Hour. 

Fasting. 

in  150  C.C. 

Water. 

in  rso  C.C. 
Water. 

c.c. 

c.c. 

C.C. 

C.C. 

1 

7 

28 

7 

6 

2 

2 

27 

7 

6 

3 

4 

28 

12 

7 

4 

3 

17 

100 

19 

5 

66 

89 

6 

22 

49. 


1  Fisher,  G.,  and  Wishart:    "Journal  of  Biological  Chemistry,"  1912,  xiii, 

2  Gilbert  and  Baudouin:    "Compt.  rend.  soc.  biol.,"  1908,  Ixv,  710. 


292  SCIENCE   OF   NUTRITION 

These  authors  also  found  that  the  hour  of  the  sudden  in- 
crease in  the  quantity  of  urine  eliminated  coincided  with  the 
completion  of  the  absorption  of  glucose  from  the  gut,  and  with 
the  last  hour  of  increased  metabolism  as  determined  in  Lusk's 
calorimeter  experiments.  These  circumstances  led  them  to 
investigate  the  hemoglobin  content  of  the  dog's  blood.  They 
discovered  that  although  at  the  end  of  the  first  hour  there  was 
no  alteration  in  this  regard,  yet  at  the  end  of  the  second  hour, 
when  between  two-thirds  and  three-quarters  of  the  ingested 
sugar  had  been  absorbed  from  the  intestine,  the  blood  usually 
became  more  dilute,  as  shown  by  a  fall  in  the  percentage 
amount  of  hemoglobin.  This  indicates  the  continuance 
of  a  generous  distribution  of  glucose  molecules  to  the  tissues 
by  means  of  an  increase  in  the  volume  of  the  nourishing 
fluid. 

With  the  cessation  of  absorption  and  the  return  of  the 
blood  to  its  normal  volume  the  metabolism  falls  to  its  basal 
level,  the  respiratory  quotient  frequently  falls,  and  there  is 
every  indication  of  a  regulation  of  the  carbohydrate  supply  to 
the  tissues  by  the  liver  so  that  fat  and  carbohydrate  are 
oxidized  together.  Only  when  this  food  supply  is  supple- 
mented by  carbohydrate  from  the  gut  does  the  metabolism 
rise.  Such  an  increase  may,  therefore,  be  properly  termed  the 
"metabolism  of  plethora."  It  was  furthermore  shown  that 
during  the  period  of  absorption  there  was  little  retention  of 
glycogen  by  the  liver — the  absorbed  glucose  apparently  passed 
freely  into  the  tissues.  The  largest  glycogen  content  of  the 
liver  was  found  during  the  last  hour  of  absorption,  the  last  of 
high  metabolism,  and  the  hour  characterized  by  passage  of  a 
large  volume  of  urinary  water.  This  was  the  hour  when  the 
liver  assumed  the  duty  of  arbiter  over  the  carbohydrate 
supply  to  the  cells. 

The  calorimetric  and  respiratory  experiments  which  estab- 
lished these  interrelations  are  portrayed  in  the  accompanying 
chart  (Fig.  20). 

The  experiments  showed  that  the  height  of  the  metabolism 


INFLUENCE    OF    THE    INGESTION    OF    CARBOHYDRATE      293 

was  about  the  same  whether  50  or  75  grams  of  glucose  were 
given,  only  in  the  latter  case  the  effect  was  more  prolonged. 
This  is  in  accord  with  Rubner's  idea  of  "self-regulation,"  and 
also  accords  with  the  fact  that  the  fermentative  activity  of 
living  yeast  cells  is  independent  of  the  concentration  of  the 
sugar  solution  in  which  they  live.1 


\ 


20  ( 
15" 

:a 

L0 

RIE 

:s 

—- 

— 

=s 

~ 

q 

... 

— 

— 

- 

r* 

— 

10 

5 

20G. 


50  G. 


NO  FOOD 


fTER    20    2I    " 

trooo 


DEXTROST 


1       i       A       S 


75  G.,        50  G.       6.7  G. 
OLIVE.  OIL    NaCl 


12  G.    200C.C. 
UREA   Water 


2   3   4  5 


Fig.  20. — Illustrating  the  effect  of  the  ingestion  of  glucose  and  fat  and  of 
water,  urea,  and  salt  solutions  on  the  metabolism.  Solid  lines — metabolism 
in  calories  as  calculated.     Broken  lines — metabolism  in  calories  as  found. 


What  is  the  cause  of  the  increased  metabolism  after  the 
ingestion  of  glucose?  In  Fig.  20  it  appears  that  the  adminis- 
tration of  150  c.c.  of  water,  either  alone  or  containing  6.7 
grams  of  sodium  chlorid  or  17  grams  of  urea,  has  no  effect 

1  Rubner:  "Sitzungsberichte  der  k.  preussischen  Akademie  der  Wissen- 
schaften,"  1013,  viii,  232. 


294 


SCIENCE    OF    NUTRITION 


upon  the  heat  production.  Therefore  neither  osmotic  ex- 
changes nor  increased  kidney  function,  nor  intestinal  absorp- 
tion can  play  any  part  in  the  increased  heat  production. 

These  experiments  led  to  further  investigations1  to  inquire 
into  the  cause  of  the  rise  in  heat  production  after  glucose 
ingestion.  To  this  end  various  carbohydrates  were  given  to 
the  same  dog  in  quantities  of  50  grams.  The  fact  that  fructose 
exerted  a  more  powerful  influence  on  metabolism  than  glucose 
was  confirmed.  It  was  also  shown  that  galactose  oxidized 
with  much  greater  difficulty  in  the  dog  than  the  other  two 
monosaccharids,  as  evidenced  by  a  lower  metabolism  and  a 
lower  respiratory  quotient,  and  that  lactose  was  not  oxidized 
at  all,  and  therefore  caused  no  increase  in  the  heat  production. 
This  latter  fact  must  have  been  due  to  the  absence  of  lactase 
from  the  intestine.  These  relations  are  shown  in  the  following 
table : 

INFLUENCE  OF  50  GRAMS  OF  VARIOUS  CARBOHYDRATES  UPON 
THE   METABOLISM  OF  THE   DOG 


Sugar  50  Gm. 

Average 
R.Q. 

2,  3,  AND  4 

Hours. 

Experiment 
No. 

Percentage  of 
Increase  Over 
Indirect  Basal 
Metabolism. 

34,  36 

64,  66,  67 

60,58 

67 
62 

Glucose 

Fructose 

1. 00 
1.02 
I.02 

o-93 

0.90 

30 
37 
34 
22 

3 

Sucrose 

Galactose 

Lactose 

Weinland2  has  shown  that  galactose  does  not  form  glycogen 
as  readily  as  do  glucose  and  fructose.  From  these  facts  it  is 
most  probable  that  galactose  does  not  as  readily  dissociate 
into  easily  oxidizable  molecules  as  do  glucose  and  fructose. 


xLusk:    "Journal  of  Biological  Chemistry,"  1915,  xx,  555. 

2  Weinland :    "Zeitschrift  fur  Biologie,"  1899,  xxxviii,  16  and  607. 


INFLUENCE    OF    THE    INGESTION    OF    CARBOHYDRATE      295 

By  similar  reasoning  one  may  explain  the  difference  in  be- 
havior between  glucose  and  fructose.  Glucose  molecules 
require  simple  dehydration  for  conversion  into  glycogen  and 
may  in  that  fashion  be  removed  from  the  tissue  fluids.  Fruc- 
tose cannot  be  thus  removed.  It  must  first  undergo  chemical 
change,  very  likely  by  fragmentation  into  methyl-glyoxal  with 
its  three-carbon  chain  (formula  on  p.  265)  before  it  can  be 
synthesized  into  glycogen.  These  molecules  being  then  in 
greater  mass  than  similar  molecules  derived  from  ingested 
glucose  would  have  been,  it  is  easy  to  conceive  that  a  higher 
metabolism  would  result  on  account  of  the  greater  plethora 
of  oxidizable  particles.  F.  G.  Benedict1  states  that  the 
cause  of  the  specific  dynamic  action  of  carbohydrates  is  the 
formation  of  acids,  which  act  as  stimuli.  In  support  of  this 
he  cites  an  experiment  by  Benedict  and  Joslin,2  in  which  an 
increase  of  30  per  cent,  in  the  heat  production  of  a  diabetic 
woman  took  place  after  the  ingestion  of  100  grams  of  fructose, 
notwithstanding  the  fact  that  the  respiratory  quotient  before 
and  after  administration  of  the  sugar  was  0.69,  indicating  that 
none  of  the  fructose  was  oxidized.  Since  fructose  is  trans- 
formed into  glucose  in  the  diabetic  organism,  Benedict  inter- 
preted this  experiment  as  indicating  the  formation  of  acid 
intennediary  products  which  stimulated  metabolism. 

Lusk  has  proved  that  when  12.5  grams  of  glycocoll,  which 
are  convertible  into  10  grams  of  glucose,  are  given  to  a  phlor- 
hizinized  dog,  the  heat  production  is  largely  increased  (see  p. 
244).  Not  so,  however,  with  fructose.  When  10  grams  of 
fructose,  which  are  convertible  into  10  grams  of  glucose,  are 
given  to  a  phlorhizinized  dog  there  is  no  increase  whatever 
in  metabolism.  The  chemical  intermediates  between  fructose 
and  glucose  are  without  stimulating  influence.  This  appears 
in  the  following  experiment: 

Benedict,.  F.  G.:  "Transactions  of  the  XVth  International  Congress  of 
Hygiene,"  191 2,  ii,  394. 

2  Benedict  and  Joslin:    "Metabolism  in  Severe  Diabetes,"  1912,  p.  69. 


296  SCIENCE   OF   NUTRITION 

THE  INFLUENCE  OF  FRUCTOSE  IN  PHLORHIZIN  GLYCOSURIA 


Conditions. 

Hours. 

Urin- 
ary 

D  :N. 

R.Q. 

Non- 
pro- 
tein 
R.Q. 

Calories. 

No. 

Pro- 
tein. 

Total 
Indi- 
rect. 

81 

Eighth    day    fasting    and 
phlorhizin 

Average 

Same  after  fructose  10  gm. 

Average 

1 

2 

2 
3 

4 

4.22 
4.22 

7-31 
7-3i 
7-3i 

0.719 
0.711 

0.715 
0.697 
0.607 
0.680 

0.692 

0-75 
0.74 

0.72 
0.73 
0.70 

7.04 
7.04 

6!o8 
6.08 
0.08 

26.57 
27.62 

27.10 
25.80 
25.80 
24.78 

25.46 

From  the  fact  that  the  ingestion  by  a  phlorhizinized  dog 
of  alanin,  which  certainly  yields  lactic  or  pyruvic  acids  in 
metabolism,  causes  a  considerable  rise  in  the  heat  production, 
(see  p.  244),  one  may  conclude  that  such  acids  are  not  inter- 
mediary metabolites  in  the  reaction  which  converts  fructose 
into  glucose. 

It  may  be  added  that  if  much  acid  be  produced  in  carbo- 
hydrate metabolism,  one  would  expect  to  find  an  increased 
quantity  of  ammonia  in  the  urine  during  the  oxidation  of 
carbohydrate,  just  as  ammonia  elimination  increases  when 
lactic  acid  is  formed  in  phosphorus-poisoning,  but  such  an 
increase  is  not  observed.1  Furthermore,  if  there  were  a  con- 
siderable production  of  acid  as  a  result  of  carbohydrate 
oxidation  one  would  expect  to  find  a  fall  in  the  quantity 
of  carbon  dioxid  in  the  blood,  such  as  occurs  after  giv- 
ing meat,  whereas  unpublished  experiments  done  by  Dr. 
A.  L.  Meyer  in  the  author's  laboratory  show  that  this  is 
not  the  case — the  quantity  of  carbon  dioxid  remains  un- 
changed. 

It  is  interesting  to  note  that  Freise2  found  that  when  a 
surviving  dog's  liver  is  perfused  with  blood  it  yields  55  to  192 

1  Murlin  and  Lusk:    "Journal  of  Biological  Chemistry,"  1915,  xxii,  15. 

2  Freise:    "Biochemische  Zeitschrift,"  1913,  liv,  474. 


INFLUENCE    OF   THE   INGESTION   OF   CARBOHYDRATE      297 

milligrams  of  carbon  dioxid  per  minute  per  kilogram  of  sub- 
stance. Addition  of  glucose,  pyruvic  acid,  lactic  acid,  or 
glyceric  acid  increases  the  carbon  dioxid  50  per  cent.,  whereas 
galactose,  glyoxylic,  glycollic,  and  acetic  acids  were  without 
influence. 

It  is,  of  course,  known  that  the  end-product  of  sugar 
metabolism,  carbonic  acid,  is  a  stimulus  to  the  respiratory 
center;  but  the  end-product  cannot  be  the  cause  of  its  own 
increased  production  for  the  following  reasons:  If  methyl- 
glyoxal  be  an  intermediate  it  may  pass,  on  the  one  hand,  back 
into  glucose,  and,  on  the  other,  forward  into  acetaldehyd 
with  the  elimination  of  carbon  dioxid. 

C6H1206— 2H2O ►  CH3.CO.CHO  +  H20 ►  CH3.CHO  +  C02  +  H2 

The  reader  is  referred  to  p.  268,  on  which  is  described  how  by 
this  process  the  transformation  of  carbohydrate  into  fat 
may  occur.  Now  if,  under  these  conditions,  there  is  a  great 
stimulation  of  metabolism,  one  would  expect  to  find  after 
giving  an  excess  of  carbohydrate  that  the  heat  production 
would  be  proportional  to  the  amount  of  fat  synthesized  in  the 
organism.  This  is  emphatically  not  true.  Neither  the  extra 
volume  of  carbon  dioxid  produced,  which  carries  the  respira- 
tory quotient  above  unity,  nor  the  extra  metabolites  involved 
in  the  reaction  are  effective  in  materially  increasing  the  heat 
production  (see  p.  308). 

It  would  seem  that  the  real  cause  of  the  increased  heat 
production  after  carbohydrate  ingestion  lay  in  the  plethora  of 
acetaldehyd  molecules,  which  the  cells,  within  the  limits  of  the 
definite  upper  level  imposed  by  self-regulation,  were  capable 
of  utilizing.  Above  this  level  the  acetaldehyd  molecules  are 
convertible  into  fat  with  little  loss  in  the  original  energy 
content  of  the  sugar  from  which  they  arise. 

The  subject  may  be  approached  from  still  another  stand- 
point, combining  the  influence  of  carbohydrate  with  that  of 
amino-acids  and  other   food-stuffs.     The  following  observa- 


298  SCIENCE    OF   NUTRITION 

tions  have  been  made  by  the  author.1  When  50  grams  of 
glucose  were  administered  to  a  dog  the  heat  production  in- 
creased 30  per  cent.;  with  70  grams,  the  increase  was  35  per 
cent.  Twenty  grams  of  glycocoll  increased  it  36  per  cent.,  and 
the  same  amount  of  alanin,  32  per  cent.  Combined,  50  grams 
of  glucose  and  20  grams  of  glycocoll  are  the  glucose  equivalent 
of  66  grams,  and  yet  when  they  were  .given  together  the  metab- 
olism increased  56  per  cent.,  an  increase  greater  than  66  grams 
of  glucose  could  have  induced.  Glucose  and  alanin  in  similar 
quantities  are  a  glucose  equivalent  of  70  grams  and  caused  an 
increase  in  heat  production  of  53  per  cent.  It  is  obvious  that 
an  increase  in  the  quantity  of  glucose  when  this  is  given  in 
large  amounts  scarcely  affects  metabolism ;  but  that  the  chem- 
ical stimulus  of  amino-acids  acting  in  conjunction  with  a 
plentiful  supply  of  glucose  results  in  a  rise  in  heat  production 
which  is  nearly  the  sum  of  the  two  individual  influences  acting 
separately.  This  points  to  a  distinct  difference  between  the 
cause  of  the  specific  dynamic  action  of  glucose  and  that  of 
alanin,  which  latter  is  convertible  into  lactic  acid  and  eventu- 
ally into  glucose. 

Lactic  acid  from  alanin  or  glycollic  acid  from  glycocoll 
may  therefore  raise  the  level  of  cell  activity  through  direct 
stimulation;  and  if  fragments  of  glucose  metabolism  be  present 
in  quantity,  these  may  enter  as  .increased  fuel  to  produce  yet 
higher  metabolism  in  the  cells  than  the  oxyacids  would  alone 
induce. 

Also,  when  alcohol  is  given  with  glucose  the  metabolism 
rises  above  the  level  it  would  have  attained  had  glucose  been 
administered  alone.  The  respiratory  quotient  falls,  the  cells 
oxidize  both  alcohol  and  the  fragments  of  glucose  metabolism, 
and  produce  almost  as  much  extra  heat  as  the  sum  of  the 
quantities  of  heat  which  each  material  would  have  induced 
alone. 

These  experiments  were  extended  by  Murlin  and  Lusk,2 

1  Lusk :    Lot.  cit. 

2  Murlin  and  Lusk:   "Journal  of  Biological  Chemistry,"  1015,  xxii,  15. 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   2 99 

so  that  the  influence  of  glycocoll,  glucose,  and  fat  when  ingested 
severally  and  together  could  be  analyzed. 

It  was  found  that  if  glucose  be  ingested  at  the  time  of  the 
highest  fat  metabolism,  the  heat  production  undergoes  a 
second  increase  to  the  same  extent  which  glucose  alone  would 
have  increased  metabolism.  At  this  level  of  higher  metab- 
olism the  respiratory  quotient  is  0.93  or  0.94,  instead  of  unity, 
which  it  would  have  been  if  glucose  had  been  given  alone, 
hence  glucose  and  fat  were  being  oxidized  together.  The 
urinary  ammonia  fell  following  the  ingestion  of  glucose  four 
hours  after  fat  ingestion,  and  this  was  true  in  spite  of  the  com- 
bined oxidation  of  fat  and  carbohydrate.  This  -does  not 
suggest  the  presence  of  acid  formation  as  the  cause  of  the 
high  metabolism. 

When  glucose  and  glycocoll  are  given  together  so  that 
their  molecules  enter  the  circulation  at  the  time  of  the  height 
of  fat  absorption,  the  increase  in  metabolism  is  very  nearly 
equal  to  the  sum  of  the  increases  which  each  of  the  three 
materials  would  have  induced  alone. 

The  following  table  and  accompanying  chart  (Fig.  21,  p. 
300)  show  these  relations: 


THE  EFFECT  OF  GLYCOCOLL,  GLUCOSE,  AND  FAT,  SEVERALLY 
AND  TOGETHER 

Dog  XIV.     Second  Series. 


Experiment  Nos. 


15,  17,  21  Basal. 


20 
18 

16,  19 
23 

24 


R.Q. 


O.86 
o.So 

O.QO 


Fat,  75  grams 

Glycocoll,  20  grams 

Glucose,  70  grams 1.0 

Glucose,  50  grams  +  glycocoll, 

20  grams 1.03 

Glucose,  50  grams  +  glycocoll, 
20  grams,  given  four  hours 
after  fat,  75  grams r.02 


Cal. 

PER 

Hour. 


22.7 
26.6 
27.6 
29.6 

33-5 


37-3 


No. 

OF 

Hours. 


Increase 

Over 
Normal. 


Cal. 

3-9 
4.9 
6.9 

10.8 
14.6 


Pr.  Ct. 

17 

25 
30 

48 
64 


*  Hours  6,  7,  8,  9  after  fat  ingestion. 


300 


SCIENCE    OF   NUTRITION 


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Fig.  21. — The  effect  of  fat,  of  glycocoll,  of  glucose,  of  glucose  4-  glycocoll) 
and  of  glucose  +  glycocoll  4-  fat  upon  the  heat  production.  (The  "glucose 
four  hours  after  fat"  curve  is  atypical,  is  not  similar  to  other  experiments,  and 
probably  denotes  a  slow  emptying  of  the  stomach). 


From  the  data  obtained  with  this  dog  the  following 
computation  may  be  made,  which  shows  that  the  sum  of  the 
individual  increases  of  heat  production  caused  by  each  sub- 
stance is  only  a  little  more  than  the  total  heat  production 
when  all  the  substances  are  given  together: 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   301 

Calories.  Per  Cent. 

Glycocoll,  20  grams 4.9  25 

Glucose,  70  grams 6.9  30 

Fat,  75  grams 3.9  17 

Sum  of  all 15.7  72 

Glycocoll,  20  gm.  +  glucose,  50  gm.,  4  hrs.  after 

fat,  75  gm 14.6  64 


A  Theory  of  Metabolism 

Rubner1  conceived  that  the  living  cell  had  essentially 
two  nutritive  affinities — one  for  fat,  the  other  for  carbohydrate. 
When,  as  in  diabetes,  the  affinity  for  carbohydrate  was  ren- 
dered inactive,  fat  alone  oxidized  for  the  maintenance  of  the 
body.     Rubner's  theory  of  metabolism  is  given  on  p.  239. 

The  more  intimate  knowledge  derived  from  the  study 
of  the  action  of  intermediary  metabolites  during  short  periods 
of  time  compels  another  viewpoint.  In  presenting  the  follow- 
ing interpretation,  the  writer  is  keenly  aware  of  the  transitory 
character  of  all  theories.2 

In  each  mammal  there  is  a  basal  metabolism.  This  corre- 
sponds with  the  minimal  heat  production  eighteen  hours  after 
taking  a  mixed  diet.  Under  these  circumstances  the  cells 
are  nourished  by  a  food  supply  of  fat  and  of  carbohydrate,  the 
latter  supply  being  regulated  by  the  liver.  The  basal  metab- 
olism may  be  acted  on  by  food  in  the  following  ways: 

(1)  Amino-acid  stimulation,  in  which  some  oxy-  or  keto- 
acids  derived  from  protein  metabolism  stimulate  the  cells  to  a 
higher  level  of  oxidative  activity. 

(2)  Fat  plethora,  in  which  an  influx  of  fat  from  the  gut 
increases  the  heat  production  at  the  expense  of  fat  itself. 
When  fat  is  oxidized  two  carbon  atoms  are  broken  from  the 

1  Rubner:   "Archiv.  fur  Hygiene,"  1908,  lxvi,  15. 

2  During  the  discussion  which  followed  the  presentation  of  papers  on  the 
subject  of  the  specific  dynamic  action  of  the  food-stuffs  at  the  International 
Congress  of  Hygiene  and  Demography  held  at  Washington  in  191 2,  Professor 
Rubner  said:  ''Ich  freue  mich  dass  die  Frage  der  'specific  dynamic  action' 
durch  neue  Untersuchungen  weiter  gefiihrt  worden  ist.  Die  Erklarungen  der 
Tatsachen  wechseln  mit  der  Zeit:  das  ist  die  Geschichte  der  Wissenschaft. 
Ich  freue  mich  constatieren  zu  konnen,  dass  meine  alten  Untersuchungen  nun 
endlich  bestatigt  worden  sind." 


302  SCIENCE   OF   NUTRITION 

chain  together.  What  form  this  cleavage  takes  is  not  known; 
it  is  usually  pictured  as  productive  of  acetic  acid.  If  palmitic 
acid  broke  up  by  successive  oxidations  into  acetic  acid  radicles, 
one  could  write  the  following  reaction: 


C16H3203     + 

'almitic  acid. 

140 

=     8C.H4O2 

Acetic  acid. 

i  gram 
9353  calories 

=           1.348  grams 
=     4706  calories 

Such  a  reaction  involves  50  per  cent,  loss  of  heat.  Perhaps 
the  energy  imparted  to  the  cell  in  fat  metabolism  is  derived 
from  a  twofold  source — acetic  acid  and  the  oxidation  at  the 
/3-carbon  atom  of  the  fatty  acid;  or  perhaps  a  substance  more 
highly  explosive  than  acetic  acid  is  set  free  as  the  result 
of  /3-oxidation.  In  any  event  one  may  conceive  of  the  oxida- 
tion of  fat  as  being  in  the  nature  of  successive  ultra-micro 
explosions,  which  act  as  power  for  the  machinery  of  the  cells. 
(3)  Carbohydrate  plethora,  in  which  an  influx  of  carbohy- 
drate from  the  intestine  increases  the  heat  production.  When 
these  enter  the  circulation  alone  they  are  oxidized  to  the  exclu- 
sion of  fat.  It  appears  certain  that  the  intermediary  metab- 
olites of  glucose  and  fructose  are  far  more  readily  oxidizable 
than  fat,  and  on  this  account,  when  they  are  present,  they 
satisfy  the  energy  requirements  of  the  cell  and  the  fat  is  not 
attacked.  If  glucose  breaks  up  into  methyl-glyoxal  and  this 
into  acetaldehyd  and  formic  acid,  the  reaction  would  be  as 
follows: 

C6Hi206-2H20   >    2C,H,Oo    +    2H2O   >    2CH..CHO    +    2HCOOH 

Glucose.  Methyl-  Acetaldehyd.1 

glyoxal. 

i  gram  0.4889  gram 

3.762  calories  3.098  calories 

According  to  this  computation,  and  assuming  that  hydro- 
lytic  reactions  are  accomplished  without  thermal  changes,  79 
per  cent,  of  the  energy  liberated  in  carbohydrate  metabolism 

1  If  the  hydrogen  in  formic  acid  were  oxidized  to  water  (HCOOH >  C02 

+  H2,  H2  +  O  =  HoO)  the  heat  evolved  would  be  0.755  calorie.     The  heat 
of  combustion  of  formic  acid  is  unknown. 


INFLUENCE    OF    THE    INGESTION    OF    CARBOHYDRATE      7>°3 

would  be  derived  from  acetaldehyd  and  21  per   cent,  from 
formic  acid. 

There  is  no  indication  of  a  physiologic  separation  of 
these  two  varieties  of  energy.  It  happens  frequently  that 
with  the  cessation  of  glucose  absorption  the  respiratory  quo- 
tient remains  at  1.00,  indicating  that  carbohydrate  is  still 
the  essential  food,  and  yet  the  metabolism  has  fallen  to  the 
basal  level.  One  must,  therefore,  conclude  that  the  metab- 
olism increases  only  in  the  presence  of  a  plethora  of  dissociated 
fragments  of  sugar.  The  metabolism  may  rise  to  a  certain 
height  which  is  not  transcended,  and  an  excess  of  metabolites 
above  this  level  may  be  converted  into  fat  (see  p.  308)  with 
scarcely  any  energy  loss. 

(4)  Carbohydrate  and  Fat  Plethora. — Here  there  is  a 
summation  of  effect.  It  seems  as  though  that  part  of  the 
cell  mechanism  which  is  susceptible  to  fat  metabolism  when 
fat  is  present  in  excess  is  not  inhibited  from  metabolizing  such 
surplus  fat  even  in  the  presence  of  carbohydrate. 

(5)  Amino-acid  Stimulation  and  Carbohydrate  and  Fat 
Plethora. — Simultaneous  ingestion  of  an  amino-acid  and 
carbohydrate  acts  in  such  a  manner  as  to  suggest  that  the 
increase  in  metabolism  due  to  carbohydrate  plethora  is  es- 
sentially independent  of  that  due  to  the  chemical  stimulus  of 
amino-acids.  Also  when  an  amino-acid  is  given  together  with 
glucose  at  the  height  of  fat  metabolism  (four  hours  after  fat 
ingestion)  the  increase  in  heat  production  is  nearly  one  amount- 
ing to  a  summation  of  the  three  influences. 

One  may,  therefore,  conclude  that  the  influence  of  food 
upon  the  quiet  resting  cell  under  these  circumstances  is  upon 
three  independent  mechanisms  within  the  cell: 

(a)  A  mechanism  which  is  receptive  to  a  chemical  stimulus 
derived  from  the  metabolism  of  such  amino-acids  as  glycocoll 
and  alanin. 

(b)  A  mechanism  of  carbohydrate  plethora  which  allows 
the  metabolism  of  carbohydrate  up  to  the  limits  imposed  by 
"self-regulation." 


304  SCIENCE   OF   NUTRITION 

(c)  A  mechanism  capable  of  receiving  power  from  that 
quota  of  fat  which  when  in  excess  increases  the  heat  produc- 
tion of  the  cell. 

THE  CONVERSION  OF  CARBOHYDRATE  INTO  FAT 

Voit,  when  he  wrote  his  "Physiologie  des  gesammt  Stoff- 
wechsels  und  der  Ernahrung,"  in  188 1,  was  unable  to  give 
definite  proofs  of  the  conversion  of  carbohydrate  into  fat  in 
the  organism,  although  such  conversion  was  popularly  believed 
to  take  place.  Definite  proof  of  the  conversion  of  carbohy- 
drates into  fat  was  afforded  by  Meissl  and  Strohmer,1  who 
gave  a  pig,  weighing  140  kilos,  2  kilograms  of  rice  containing 
1592  grams  of  starch  daily  for  seven  days,  and  collected  the 
carbon  and  nitrogen  of  the  excreta  by  means  of  a  Pettenkofer- 
Voit  apparatus  during  two  days  of  the  period.  The  average 
results  per  day  were  as  follows: 

Carbon,  Nitrogen, 

Grams.  Grams. 

Ingested  in  food 765.37  18.67 

Excreted 476.15  12.59 

Balance  retained  in  the  body 289.22  6.08 

The  nitrogen  retained  represented  38  grams  of  protein 
containing  20.1  grams  of  carbon;  269.12  grams  of  retained 
carbon  were  therefore  available  for  glycogen  or  fat  construc- 
tion. Since  the  amount  of  carbon  retained  exceeded  the  pos- 
sible glycogen  formation,  fat  must,  therefore,  have  been  added 
to  the  body.  Had  all  the  carbon  retained  been  converted  into 
fat  it  would  represent  a  production  of  343.9  grams  of  fat.  Of 
this  only  33.6  grams  of  fat  could  have  arisen  from  the  protein 
metabolism  of  the  period.  Hence  it  is  possible  that  310.3 
grams  of  fat  may  have  originated  from  1592  grams  of  starch 
ingested,  which  indicates  a  conversion  of  19.5  per  cent,  of  the 
starch  given  into  fat. 

Similar  experiments  were  made  with  geese  by  E.  Voit  and 

1  Meissl  and  Strohmer:  "Sitzungsberichte  der  k.  Akad.  d.  Wissenschaften," 
1883,  lxxxviii,  III  Abtheilung. 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   305 

C.  Lehmann.1     The  geese  were  starved  four  and  a  half  days 
and  were  then  fed  with  rice. 

One  of  these  respiration  experiments  which  lasted  thirteen 
days  has  been  published,2  and  is  as  follows: 

Nitrogen.  Carbon. 

In  the  2609  grams  of  rice 41 .47  H59-7 

In  the  excreta — 

Urine  and  feces 45-39  134-8 

Respiration 657.8 

Total 45-39  792-6 

Change  in  the  body —  3.92  +367.1 

At  the  commencement  of  the  experiment  the  animal 
weighed  4  kilograms.  There  was  no  protein  retention,  but  31 
per  cent,  of  the  carbon  ingested  was  not  eliminated.  The 
protein  metabolism  could  not  yield  nearly  enough  carbon  to 
account  for  that  retained.  As  the  rice  contained  but  0.51 
per  cent,  of  ether  extract,  the  retained  carbon  could  not  have 
been  administered  in  the  form  of  fat.  If  367.3  grams  of  carbon 
had  been  retained  in  the  form  of  glycogen  this  would  have 
aggregated  851  grams,  or  20  per  cent,  of  the  whole  goose, 
or  the  starch  content  of  a  potato.  This  is  a  manifest  impossi- 
bility, since  E.  Voit3  found  only  2.2  per  cent,  of  glycogen  in  a 
goose  which  had  been  largely  fed  on  rice.  Since  the  carbon 
retained  could  not  have  been  stored  as  glycogen,  the  only 
alternative  remaining  is  to  assume  its  retention  as  fat. 

Rubner  about  the  same  time  showed  the  same  principles 
to  be  true  in  the  case  of  the  dog. 

It  is  evident,  then,  that  pigs,  geese,  and  dogs  can  convert 
carbohydrates  into  fat.  The  fattening  of  cattle  may  be 
similarly  accomplished. 

The  ability  to  convert  carbohydrate  into  fat  probably 
exists  throughout  the  animal  kingdom.  Thus  Weinland4  has 
expressed  from  living  ascaris  ferments  which  convert  glycogen 

1  Voit:  "Sitzungsberichte  der  kgl.  bayr.  Akad.  d.  Wissenschaft,"  1885,  p. 
288. 

2  Lehmann  and  E.  Voit:   "Zeitschrift  fur  Biologie,"  1901,  xlii,  644. 

3  E.  Voit:   Ibid.,  1889,  xxv,  543. 

4  Weinland:  Ibid.,  1901,  xlii,  55;  1902,  xliii,  86;  1904,  xlv,  113. 


306  SCIENCE   OF   NUTRITION 

into  glucose  and  then  into  valerianic  and  possibly  caproic 
acids — 0.8  gram  of  dextrose  yields  0.3  gram  of  valerianic 
acid. 

This  is  suggestive  of  a  wide-spread  biologic  capability. 

When  carbohydrates  are  converted  into  fat  in  the  organism 
the  respiratory  quotient  (volume  or,  see  P-  57)  maY  rise  verY 
considerably  above  unity.  This  is  for  the  reason  that  an 
oxygen-rich  substance  like  glucose  is  being  converted  into 
substance  which  is  poor  in  oxygen.  Hence  the  volume  of 
expired  carbon  dioxid  may  be  greater  than  the  volume  of 
inspired  oxygen.  Max  Bleibtreu1  found  that  the  respiratory 
quotient  of  a  goose  which  had  been  stuffed  with  grain  was  1.33, 
whereas  the  same  goose  when  fasting  showed  a  normal  quotient 
for  that  condition  of  0.728.  Pembrey2  describes  how  marmots 
previous  to  the  winter  hibernation  instinctively  devour  large 
quantities  of  carbohydrate  food,  and  how  the  respiratory 
quotient  may  rise  even  as  high  as  1.39.  This  indicates  a  fat 
production  for  use  during  the  winter. 

Grafe3  gave  to  a  fasting  dog  three  times  his  daily  caloric 
requirement  of  energy  in  the  form  of  carbohydrate,  and  noted 
an  increase  of  33  per  cent,  in  the  heat  production  and  a  maxi- 
mal non-protein  respiratory  quotient  of  1.3 1.  A  discussion 
of  the  intermediary  chemical  reactions  involved  in  this  process 
has  already  been  given  (see  p.  268).  Written  in  their  simplest 
formulae  the  production  of  butyric  or  of  palmitic  acids  from 
glucose  would  read: 

C«Hi20«    +    02    =    C4H802      +    2CO2    +    2H20 
4C6H120     +     02     =     Cir,H3202     +     8CO2     +     8H20 

One  may  accept  Bleibtreu's  formula  as  the  simplest 
expression  of  the  conversion  of  carbohydrate  into  fat,  as 
follows: 

270.6  gm.  glucose  =  100  gm.  fat  +  115.45  gm.  C02  +  54-6  gm.  H20 
997.2  calories  =  950.0  calories. 

1  Bleibtreu:  "Pfluger's  Archiv,"  1901,  Ixxxv,  345.^ 

2  Pembrey:  "Journal  of  Physiology,"  1901,  xxvii,  407. 

3  Grafe:   "Deutsch.  Archiv  fur  klin.  Med.,"  1914,  cxiii,  1. 


INFLUENCE  OF  THE  INGESTION  OF  CARBOHYDRATE   307 

The  reaction  is  evidently  exothermic,  4.7  per  cent,  of  the  heat 
being  liberated.  If  the  heat  evolved  be  measured  on  the 
basis  of  the  extra  carbon  dioxid  production,  1  liter  of  such 
carbon  dioxid  would  have  a  value  of  0.8  calorie,  or  less  than 
one-sixth  the  caloric  equivalent  of  a  liter  of  carbon  dioxid 
obtained  from  the  oxidation  of  glucose  in  the  ordinary  manner. 
On  the  basis  of  this  the  heat  production  of  a  dog  after 
giving  70  grams  of  glucose  was  calculated  in  experiments 
performed  by  Lusk.1  The  results  of  two  of  the  three  experi- 
ments are  presented  in  the  accompanying  table : 

DOG  III.     METABOLISM  AFTER  GIVING  70  GRAMS  OF  GLUCOSE 
IN   210   C.C.   OF  WATER   AT  38° 


Experiment 

88. 

Experiment  gi. 

Hours. 

Non- 
protein 
R.Q. 

Indirect 
Uncor- 
rected. 

Indirect       n;      . 
Corrected.     direct. 

Non- 
protein 
R.Q. 

Indirect 
Uncor- 
rected. 

Indirect 
Corrected. 

Direct. 

4 

1.03 

1. 11 

1. 12 

Calories. 

25-24 
24.89 
24.82 

Calories. 

25-34 
25.26 

25.21  _ 

Calories. 

26.12 

25-83 
24.86 

I.08 
1. 14 
1. 16 

Calories. 
24.52 
24.91 
24.98 

Calories. 
24.78 
25-38 
25-49 

Calories. 

25-31 
25-63 
25.12 

74-95 

75-8i 

76.81 

74.41 

75-65 

76.06 

That  the  method  of  calculation  of  indirect  calorimetry  in 
the  presence  of  respiratory  quotients  above  unity  is  correct 
may  be  deduced  from  these  experiments.  The  "uncorrected" 
heat  values  represent  calculations  based  on  the  oxygen  absorp- 
tion alone,  while  the  "corrected"  values  are  those  in  which  the 
quantity  of  C02  eliminated  in  excess  of  a  non-protein  respira- 
tory quotient  of  unity  is  given  a  value  of  0.803  calorie  per 
liter. 

It  is  evident  that  after  a  large  ingestion  of  glucose  direct 
and  indirect  calorimetry  agree  closely  if  the  heat  value  of  the 
carbon  dioxid  which  is  evolved  in  the  intermediary  trans- 
formation of  carbohydrate  into  fat  be  taken  into  consideration. 

1  Lusk:    Loc.  cit. 


308  SCIENCE    OF   NUTRITION 

During  the  first  three  hours  of  Experiments  88,  90,  and 
91  the  calculated  heat  production  was  75.81,  75.30,  and  75.64, 
while  the  C02  excretion  in  excess  of  a  non-protein  respiratory 
quotient  of  1.00  was  1.07,  0.80,  and  1.73  liters;  it  is,  there- 
fore, apparent  that  the  intensity  of  metabolism  is  not  related 
to  the  height  of  the  respiratory  quotient.  The  transformation 
of  carbohydrate  into  fat  takes  place  with  the  liberation  of 
very  little  energy,  and  the  height  of  the  total  metabolism  is 
scarcely  affected  by  the  process. 


CHAPTER  XI 

THE  INFLUENCE  OF  MECHANICAL  WORK  ON 
METABOLISM 

In  the  account  of  metabolism  during  starvation  a  short 
description  has  already  been  given  of  the  influence  of  mechan- 
ical work  on  protein  metabolism,  of  the  influence  of  pos- 
ture on  general  metabolism,  and  of  the  relation  of  the 
amount  of  metabolism  to  the  diurnal  variations  of  human 
temperature. 

The  source  of  mechanical  work  must  be  from  metabolism, 
for  mechanical  energy  cannot  be  derived  from  nothing.  The 
necessary  energy  might  be  obtained  in  one  of  two  ways,  either 
at  the  expense  of  a  proportionate  reduction  in  the  quantity  of 
heat  liberated  by  the  resting  organism,  or  by  an  increase  in  the 
amount  of  the  metabolism.  In  the  former  case  work  would 
diminish  the  heat  production  and  might  cool  the  tissues,  which 
is  not  observed  to  take  place.  If  work  were  done  at  the 
expense  of  increased  metabolism,  and  if  this  increase  were 
completely  converted  into  mechanical  effect,  then  the  heat 
production  in  the  organism  might  remain  the  same  as  in  the 
resting  state.  If,  however,  the  result  of  mechanical  effort 
be  a  stimulation  of  metabolism  to  the  extent  of  not  only 
enabling  the  body  to  do  work  but  also  causing  it  to  produce 
more  heat  than  when  at  rest,  then  the  tendency  of  the  tissues 
must  be  to  grow  warmer,  perhaps  with  a  resulting  outbreak 
of  sweat  to  reduce  the  body  temperature  through  physical 
regulation.     The  last  named  is  the  actual  process. 

Lavoisier's  discovery  that  the  absorption  of  oxygen  is  in- 
creased during  mechanical  exercise  firmly  established  the  fact 
of  a  higher  metabolism  under  these  conditions. 

309 


3IO  SCIENCE   OF   NUTRITION 

The  first  experiments  in  which  the  effect  of  work  upon  the 
total  metabolism  was  demonstrated  were  made  upon  a  man  by 
Pettenkofer  and  Voit.1  A  man  turned  an  ergostatic  wheel 
7500  revolutions  on  each  working  day  for  a  period  of  nine 
hours,  which  afforded  sufficient  exercise  to  cause  great  fatigue 
at  the  end  of  the  day.  The  experiments  were  made  both 
during  hunger  and  when  the  man  was  ingesting  a  medium 
mixed  diet.     The  food  supplied  in  the  mixed  diet  contained: 

Grams.  Calories. 

Protein 121. 7  506 

Fat 117.  1088 

Carbohydrates 352.  1443 

Total 3037 

The  metabolism  of  this  man,  a  strong  workman,  weighing 
70  kilograms,  at  rest  and  at  work,  starving  or  on  the  me- 
dium mixed  diet  as  given  above,  is  presented  in  the  following 
table:2 

EFFECT    OF    MECHANICAL    WORK    ON    METABOLISM    IN    MAN 


Grams  Metabolized. 

Cal.  of 
Metab- 
olism. 

Cal. 

ABOVE 

Fasting 
Quantity. 

Experiment 
No.  of  Pet- 
tenkofer 
and  Voit. 

Protein. 

Fat. 

Car- 
bohy- 
drates. 

Starvation — Rest 

—Rest 
—Work..  .  . 

70.8 
68.7 
66.1 

222 
208 
387 

2374 
2231 
3882 

1582 

I 
III 
IV 

Mixed  diet — Rest .... 
—Rest. . . . 
—Rest.... 
—Work... 
—Work .  .  . 

121. 7 
118.7 
125.0 
121. 7 
122.0 

73 

93 

84 

208 

152 

352 
352 
352 
352 

352 

2638 
2714 
2750 
3856 
3378 

330 

412 

458 

1554 

1076 

V 

VI 

VII 

VIII 

IX 

1  Pettenkofer  and  Voit:    "Zeitschrift  fur  Biologie,"  1866,  ii,  537. 

2 1  have  multiplied  the  nitrogen  of  the  ingesta  and  excreta  by  6.25  to  obtain 
the  quantity  of  the  protein  given  and  metabolized.  The  ratio  N  :  C  =  1  :  3.28 
in  protein  has  been  employed.  The  dry  starch  has  been  calculated  as  con- 
taining 44.2  per  cent,  and  the  fat  as  containing  76.5  per  cent,  of  carbon,  which 
were  the  figures  used  by  Pettenkofer  and  Voit.  Rubner's  standard  calori- 
metric  values  have  been  used.     (See  Introductory  Chapter.) 


INFLUENCE    OF   MECHANICAL   WORK   ON  METABOLISM     311 

From  these  early  experiments  it  was  evident  that  mechan- 
ical work  did  not  increase  protein  metabolism  even  in  starva- 
tion, but  that  the  power  to  do  work  might  readily  be  supplied 
by  the  increased  metabolism  of  fat. 

In  the  ear  her  editions  of  this  book  (1906  and  1909),  the 
question  was  asked  whether  energy  evoked  by  the  specific 
dynamic,  action  of  the  food-stuffs  could  be  utilized  in  the 
production  of  mechanical  work. 

The  following  experiments  by  Rubner1  show  beautifully 
that  there  is  a  summation  of  junction  as  regards  the  extra  heat 
production  due  to  the  specific  dynamic  action  of  protein  and  the 
extra  heat  production  iticident  to  mechanical  work: 

THE  INFLUENCE  OF  DIET  AND  MECHANICAL  WORK  UPON  THE 
METABOLISM   OF  A  MAN  61-63   KG.   IN  WEIGHT 


Calories  Produced. 

Heat  Loss. 

Diet  and  Conditions. 

Twenty- 
four 
Hours. 

Increase. 

Increase 
Due  to 
Work. 

Evap. 
H20. 

Rad.  and 
Cond. 

Work. 

No  food,  rest 

Calories. 
1976  . 

2023 

2868 

2515 

3370 

Per  Cent. 

+    2.4 

+  45-2 
+  27.2 

+  70-5 

Calories. 

845 

855 

Calories. 
380 

529 

907 

614 

I23S 

Calories. 
1596 

1494 

1727 

1901 

1901 

Calories. 

Cane-sugar  600  gms.  + 
H2O  3000  gms.,  rest.. 

Same  +  work   (100,000 
kg.) 

234 

234 

Protein,  large  amount  of 
meat,  rest 

Protein,   same  diet,   + 
work  (100,000  kg.) .  . 

Rubner  observed  that  mechanical  work  was  performed  with 
greater  ease  when  cane-sugar  was  the  basis  of  the  diet  than 
when  protein  was  given.  The  temperature  of  the  chamber  in 
which  the  experiments  were  performed  was  about  200  and  the 
humidity  was  about  40  per  cent.  Rubner  calls  especial  at- 
tention to  the  fact  that  when  cane-sugar  was  given  the  in- 
creased heat  produced  by  the  body  was  lost,  partly  by  the 
increased  evaporation  of  water  (62  per  cent,  of  the  increased 

1  Rubner:  "Sitzungsberichte  der  preussischen  Akademie  der  Wissen- 
schaften,"  1910,  xvi,  316. 


312  SCIENCE   OF   NUTRITION 

heat  production)  and  partly  by  an  increase  in  radiation  and 
conduction  from  the  skin  (38  per  cent,  of  the  increased  heat 
production),  whereas  after  meat  had  been  given  the  elimina- 
tion of  the  entire  extra  heat  production  due  to  work  was  thrown 
upon  the  activity  of  the  sweat-glands.  A  high  protein  dietary 
is  therefore  contraindicated  in  athletic  contests,  especially 
when  the  weather  is  hot  and  humid. 

The  100,000  kilogrammeters  of  work  described  above 
were  produced  by  the  action  of  the  arms  upon  an  ergostat. 
Since  this  quantity  of  work  is  the  mechanical  equivalent  of 
234  kilo-calories,  and  since  850  extra  calories  of  metabolism 
were  invoked  in  its  accomplishment,  it  is  evident  that  the 
mechanical  efficiency  of  the  human  engine  under  these  cir- 
cumstances was  §^>  or  27.5  per  cent. 

Benedict  and  Murschhauser1  confirm  the  summation  of 
energy  increase  from  food  and  work  in  the  case  of  men  walking 
in  a  horizontal  direction. 

Recent  investigations  in  my  laboratory,  however,  indicate 
that  a  small  dog,  accomplishing  a  given  amount  of  mechanical 
work,  shows  nearly  the  same  heat  production  without  food  as 
after  the  ingestion  of  70  grams  of  glucose.  This  is  an  impor- 
tant fact. 

Rubner2  shows  that  a  man  of  70  kilograms  weight,  devel- 
oping mechanical  energy  to  the  extent  of  15,000  kilogram- 
meters  per  hour,  produces  practically  the  same  quantity  of 
carbon  dioxid,  no  matter  what  the  temperature  of  his  environ- 
ment may  be.     The  results  of  the  experiment  are  as  follows: 


Percentage 

Carbon  Dioxid 

Water  Ex- 

Temperature 

Moisture  in 

per  Hour 

creted  per  Hour 

of  the  Air. 

the  Air. 

in  Grams. 

in  Grams. 

7-4° 

81 

84.0 

58.0 

12.70 

84 

78.5 

70.8 

16.70 

59 

97.0 

138.1 

17-5° 

87 

84.5 

90.4 

18.80 

83 

81.2 

112.8 

25.00 

47 

78.7 

230.0 

1  Benedict,  F.  G.,  and  Murschhauser:    "Energy  Transformations  During 
Horizontal  Walking,"  Carnegie  Institution  Publication  231,  1915,  p.  91. 

2  Rubner:  Von  Leyden's  Handbuch,  "Die  Ernahrungstherapie,"  1903,  Bd.  i, 
P-  74- 


INFLUENCE    OF   MECHANICAL   WORK   ON   METABOLISM     313 

This  person  while  at  rest  and  at  a  temperature  of  21.10  ex- 
creted 33.6  grams  of  carbon  dioxid  and  42  grams  of  water. 

It  is  clear  that  during  work  the  metabolism  is  indepen- 
dent of  surrounding  temperature  or  climatic  conditions. 
In  other  words,  during  mechanical  work  the  influence  of  the 
"chemical  regulation'''  of  body  temperature  may  be  eliminated 
(seep.  134).  The  extra  heat  production  in  doing  mechanical 
work  is  utilized  instead  of  the  production  of  heat  which  is 
excited  reflexly  through  cold.  These  results  were  forecast  by 
Voit.1 

Generally  speaking,  neither  clothing  nor  temperature 
affects  the  amount  of  the  metabolism  during  exercise.  They 
influence  only  the  quantity  of  water  eliminated  in  the  per- 
spiration, in  the  effort  of  the  body  to  -maintain  its  "normal 
temperature  through  physical  regulation.  It  is  evident  from 
Rubner's  details  of  the  water  excretion  that  at  a  low  temper- 
ature the  extra  heat  production  during  mechanical  exercise  is 
lost  by  radiation  and  conduction.  Rubner  explains  that  the 
slight  increase  in  the  excretion  of  water  above  that  lost  while 
at  rest  is  due  to  its  increased  evaporation  through  increased 
respiratory  activity.  At  a  higher  temperature  conduction 
and  radiation  become  insufficient  to  cool  the  body,  and  a 
large  proportion  of  the  loss  of  heat  takes  place  at  the  expense 
of  the  evaporation  of  sweat. 

In  hot,  moist  climates,  however,  the  cooling  of  the  body 
through  the  evaporation  of  moisture  becomes  difficult,  and 
this  is  especially  pronounced  in  the  case  of  fat  people  (p.  147), 
who  with  difficulty  discharge  the  heat  produced  within  them. 
Broden  and  Wolpert2  show  the  effect  of  the  action  of  temper- 
ature and  humidity  on  the  metabolism  of  a  fat  man,  weighing 
1 01  kilograms,  who  executed  the  same  amount  of  mechanical 
work  under  various  conditions  of  experimentation.  The  work 
was  light,  being  5375  kilogrammeters  per  hour.  The  results 
were  as  follows: 

1  Voit:   "Zeitschrift  fiir  Biologie,"  1878,  xiv,  152. 

2  Broden  and  Wolpert:   "Archiv  fiir  Hygiene,"  1901,  xxxix,  298. 


3i4 


SCIENCE   OF   NUTRITION 


EFFECT  OF  WORK,  TEMPERATURE,   AND   HUMIDITY  ON  THE 
METABOLISM   OF   A   FAT   INDIVIDUAL 


Grams  per  Hour. 

Temperature. 

Dry  Air. 

Humid  Air. 

CO2  in  Grams 
per  Hour. 

H2O  in  Grams 
per  Hour. 

CO2  in  Grams 
per  Hour. 

H2O  in  Grams 
per  Hour. 

47-8 
47-3 
5°-3 

319+38  gm. 
sweat. 

46.4 
48.O 
60.7 

28-300 

269 

+ 

266  gm. 
sweat. 

This  individual  was  the  same  already  mentioned  (p.  147), 
and  the  explanation  given  there  is  equally  applicable  here.  In 
a  dry  climate  the  same  amount  of  mechanical  work  may  be 
accomplished  by  a  fat  person  at  both  200  and  300  without 
changing  the  metabolism.  At  a  temperature  of  370  the  metab- 
olism rises,  for  the  cooling  power  of  the  evaporating  sweat  does 
not  seem  sufficient  to  act  through  the  dense  covering  of  fat. 
This  action  is  intensified  in  moist  air,  where  the  evaporation  of 
water  is  hindered.  Under  these  latter  conditions  the  small 
amount  of  work  was  accomplished  only  at  the  expense  of 
great  discomfort  and  profuse  perspiration. 

The  obese,  therefore,  work  under  great  disadvantage  in  a 
hot,  and  especially  in  a  hot  and  moist,  climate.  The  profuse 
perspiration  explains  their  desire  for  water  to  drink. 

In  the  early  experiments  of  Pettenkofer  and  Voit,  already 
cited,  it  was  shown  that  work  did  not  raise  the  protein  metab- 
olism even  in  starvation,  and  that  the  source  of  the  power 
appeared  to  be  the  increased  combustion  of  the  non-nitrog- 
enous fat. 

In  other  experiments  a  slight  rise  in  the  nitrogen  metab- 
olism, continuing  into  the  day  following  work,  has  been  noted. 
The  protein  metabolism,  however,  is  not  sufficient  to  yield  the 
energy  necessary  for  a  hard  day's  work.     In  the  well-known 


INFLUENCE    OF   MECHANICAL   WORK   ON  METABOLISM     315 

experiments  of  Fick  and  Wislicenus1  the  authors  climbed  the 
Faulhorn,  in  Switzerland,  a  mountain  1956  meters  high.  The 
product  of  their  weight  into  the  height  to  which  they  raised 
themselves  gave  them  a  close  approximation  to  the  amount 
of  the  work  done.  The  experimenters  took  their  last  nitrog- 
enous food  seventeen  hours  before  starting  on  their  walk. 
They  climbed  for  six  hours  and  collected  the  urine  of  this 
period  and  that  of  seven  hours  thereafter.  Their  results  were 
as  follows: 


Fick 

Wislicenus. 


Urinary 

N  of  13      Dynamic  Value 

Hours,        of  N  in  Kgm. 

Grams. 


5-74 
5-54 


63,378 
61,280 


Body 

Weight, 

Kgm. 


66 

76 


Height  of 
Faulhorn. 


1956  meters. 
1956 


Work  in 
Kgm. 


129,096 
148,656 


The  work  accomplished  represents  three  times  the  energy 
liberated  from  the  protein  metabolism  of  the  time.  The 
output  of  energy  as  measured  above  was  not  all  the  increase  in 
the  amount  of  mechanical  energy  during  the  period,  for  the 
heart  and  respiratory  muscles  acted  with  greater  force,  and 
energy  was  expended  by  swinging  the  arms  and  by  friction  on 
the  road. 

The  fact  observed  by  Pettenkofer  and  Voit  that  protein 
metabolism  may  not  be  appreciably  affected  during  mechanical 
work  has  been  abundantly  confirmed  by  Krummacher.2  A 
porter,  weighing  79  kilograms,  was  given  a  diet  containing  3700 
calories,  14.28  grams  of  protein  nitrogen,  and  a  large  amount 
of  carbohydrate.  The  man  turned  a  dynamometer  and 
produced  402,000  kilogramme  ters  of  work.  The  slight 
increase  in  protein  metabolism  could  have  yielded  but  3 
per  cent,  of  the  energy  required  for  the  work.  Krummacher 
states  that  protein  metabolism  may  increase  during  work  only 
when   the   non-nitrogenous   fat  and   carbohydrates   become 


1  Fick  and  Wislicenus:   "Myothermische  Untersuchungen," 

2  Krummacher:   "Zeitschrift  fur  Biologie,"  1896,  xxxiii,  108. 


316  SCIENCE   OF   NUTRITION 

less  available  in  metabolism.  We  have  already  seen  that 
protein  metabolism  rises  in  the  absence  of  carbohydrates. 
It  may  be  that  with  the  exhaustion  of  carbohydrates  during 
exercise  a  period  ensues  when  the  loss  of  their  influence  leads 
to  an  increased  protein  destruction.  The  larger  the  quantity 
of  carbohydrates  given,  the  less  marked  would  be  this  influence. 
It  is  interesting  in  this  connection  that  soldiers  when  starting 
on  a  march  may  have  a  high  respiratory  quotient  (indicating 
the  combustion  of  carbohydrates) ,  which  falls  at  the  end  of 
the  march  (fat  combustion)  and  which  may  remain  lower  than 
at  first,  even  on  a  day  following  the  march.1  The  fact  that 
mechanical  work  may  be  accomplished  at  the  expense  of  an 
increased  combustion  of  fat  and  carbohydrates  should  not 
cause  one  to  forget  that  protein  may  become  the  sole  source 
of  energy  in  the  body.  It  has  already  been  shown  that  a 
fasting  animal,  after  burning  all  his  fat,  may  maintain  his  life  on 
protein  alone  (see  p.  101),  and  that  Pfliiger  kept  a  dog  in  active 
condition  on  meat  alone.  As  protein  may  yield  58  per  cent, 
of  sugar  this  substance  may  still  be  the  principal  source  of 
energy. 

The  following  experiment  not  only  indicates  the  fully 
proved  point  that  muscular  work  does  not  increase  protein 
metabolism,  but  it  also  shows  that  the  character  of  the  protein 
metabolism  is  unchanged  by  muscular  activity.  Shaffer2  has 
given  a  man  a  diet  which  was  free  from  purins  and  which 
contained  only  5.9  grams  of  nitrogen.  The  individual  spent 
the  greater  part  of  six  days  in  bed  as  a  rest  period  (I).  He 
then  occupied  himself  for  five  days  with  laboratory  work, 
which  gave  a  normal  period  (II) .  During  a  final  period  (III) 
of  four  days  he  worked  in  the  laboratory  and  performed  in  ad- 
dition such  mechanical  work  as  that  of  walking  10  miles. 
The  average  of  the  analyses  of  the  urines  of  the  three  periods 
are  given  below: 

1  Zuntz  and  Schumburg:    "Physiologie  des  Marsches,"  1901. 

2  Shaffer:   "American  Journal  of  Physiology,"  1908,  xxii,  445. 


INFLUENCE   OF   MECHANICAL   WORK   ON   METABOLISM      317 

UNCHANGED   CHARACTER  OF  THE   URINE  AFTER  MUSCULAR 

WORK 


Food. 

Urine. 

Period. 

N. 

Calor- 
ies. 

Nitrogen  as: 

Sulphur. 

Total. 

Am- 
monia. 

Crea- 
tinin. 

Uric 
Acid. 

Rest. 

Total. 

I.  Rest 

5-9 
6.0 

5-9 

2300 
3000 
3200 

4-77 
4.40 

3-94 

o-35 
O.38 
O.42 

O.605 

O.60 

O.56 

O.II 

0.106 
O.I2 

o-35 
0.42 
0.42 

O.438 
O.424 
O.414 

II.  Normal.....  .  .  . 

III.  Work 

Shaffer  concludes  that  if  sufficient  food  be  allowed,  an 
increase  or  decrease  of  muscular  activity  has  no  effect  on  pro- 
tein metabolism  as  indicated  by  the  various  quantities  of 
nitrogenous  end-products  which  appear  in  the  urine.  Shaffer 
agrees  with  Van  Hoogenhuyze  and  Verploegh1  that  with  ade- 
quate nourishment  the  creatinin  elimination  is  unaffected  by 
muscular  work. 

Kocher2  states  that  doubling  the  heat  production  of  the 
day  as  brought  about  by  walking  60  kilometers  (37.5  miles), 
i.  e.,  from  Munich  to  the  Starnberger  See  and  back,  has  little 
or  no  influence  upon  the  protein  metabolism  of  men,  whether 
the  diet  consists  of  starch,  sugar  and  cream,  or  of  meat  and 
fat  without  carbohydrates. 

Bornstein3  reports  continual  retention  of  ingested  protein 
during  seventeen  days'  work,  at  a  time  when  only  protein  was 
administered.  The  quantity  of  protein  given  was  large, 
containing  19.96  grams  of  N,  and  the  daily  work  accomplished 
was  moderate,  being  17,000  kilogramme ters.  The  nitrogen 
retention  amounted  to  1.475  grams  daily,  or  an  addition  of  800 
grams  of  "flesh"  to  the  body  in  seventeen  days. 

Loewy4  reaches  the  same  conclusion  that  long-continued 


1  Van    Hoogenhuyze    and    Verploegh:     "Zeitschrift    fur    physiologische 
Chemie,"  1905,  xlvi,  415. 

2  Kocher:    "Deutsches  Archiv  fiir  klinische  Medizin,"  1914,  cxv,  82. 

3  Bornstein:   "Pfliiger's  Archiv,"  1901,  Lxxxiii,  540. 

4  Loewy:   "Archiv  fiir  Physiologie,"  1901,  p.  299. 


318  SCIENCE   OF   NUTRITION 

muscular  exercise  favors  protein  retention.  This  suggests  the 
basis  of  muscular  hypertrophy  due  to  physical  exercise. 

Large  protein  ingestion,  however,  is  not  apparently  es- 
sential to  the  full  maintenance  of  physical  power.  This  has 
been  shown  by  Chittenden,1  who  maintained  soldiers  and 
athletes  in  physical  training  for  months  at  a  time  on  diets 
containing  between  7  and  10  grams  of  nitrogen,  or  about 
half  what  the  average  man  takes  if  the  question  be  left  to  his 
taste  (see  p.  338). 

It  is  evident  that  the  power  to  accomplish  muscular 
work  is  not  usually  derived  from  protein  metabolism,  but 
from  the  combustion  of  the  non-nitrogenous  sugar  and 
fat. 

Therefore,  physical  exercise  requiring  fat  consumption 
without  concomitant  destruction  of  protein  must  be  of  the 
greatest  value  in  the  treatment  of  obesity. 

The  problem  at  once  arises:  What  is  the  relative  value  of 
fats  and  carbohydrates  as  fuel  for  the  production  of  mechanical 
energy  by  the  body? 

Zuntz,2  from  experiments  made  by  Heineman,  calculates 
that  when  carbohydrates  predominate  in  a  man's  diet  an 
amount  of  energy  above  the  resting  requirement  is  liberated 
which  equals  9.33  calories  for  every  kilogrammeter  of  work 
accomplished,  whereas,  when  fat  is  given,  10.37  calories  are 
liberated  in  the  performance  of  the  same  amount  and  the  same 
kind  of  work.  The  work  was  done  by  turning  the  wheel  of  an 
ergostat.  Since  one  kilogrammeter  is  the  mechanical  equiv- 
alent of  2.35  calories,  it  is  evident  that  25  per  cent,  of  the 
total  excess  of  energy  developed  by  work  is  convertible  into 
mechanical  effect,  the  balance  being  dissipated  as  heat. 
Similar  experiments  made  by  Zuntz  on  himself  showed  that 
9.39  and  9.33  calories  of  metabolism  were  liberated  on  a  fat 
diet,  10.37  and  10.41  on  a  carbohydrate  diet,  when  one  kilo- 
grammeter of  work  was  accomplished. 

1  Chittenden:   "Physiological  Economy  in  Nutrition,"  1904. 

2  Zuntz:   "Pfluger's  Archiv,"  1900,  lxxxiii,  557. 


INFLUENCE    OF   MECHANICAL   WORK   ON   METABOLISM     319 

There  seems  to  be  little  difference  in  the  efficacy  of  the 
body  as  a  machine,  whether  fat  or  carbohydrates  are  used  as 
fuel. 

Heineman1  remarks  that  Chauveau's  idea  that  fat  must  be 
first  converted  into  sugar  before  being  available  for  mechanical 
work  can  scarcely  be  valid,  for  such  a  conversion  of  fat  carbon 
into  sugar  would  entail  a  minimum  loss  of  29  per  cent,  of  the 
energy  available  for  mechanical  work. 

Atwater  and  Benedict2  thought  that  they  had  confirmed 
these  results,  although,  unfortunately,  the  diets  provided  were 
not  strictly  fat-protein  and  carbohydrate-protein,  but  were 
really  mixed  diets. 

Thus  J.  C.  W.,  during  two  periods  of  twenty- two  days  each, 
ingested  day  by  day  diets  which  produced  the  following 
metabolism  as  calculated  from  the  body's  excreta: 

CALCULATED   METABOLISM 

Period  I.  Period  II. 

Carbohydrate  Diet.  Fat  Diet. 

Protein 434  calories.  489  calories. 

Fat 1288       "  3190       " 

Carbohydrates 3371       "  1465       " 

Total  metabolism 5093  5144 

The  average  of  work  accomplished  and  body  heat  evolved 
each  day,  as  measured  in  the  Atwater  calorimeter,  were  as 
follows: 

WORK  AND  METABOLISM  AS  DIRECTLY  MEASURED 

Carbohydrate  Diet.  Fat  Diet. 

Mechanical  work 543  calories.  550  calories. 

Body  heat 4593       "  4555       " 

Total  metabolism 5136  5io5 

The  work  was  done  on  a  stationary  bicycle.    It  is  evident  that 
the  work  could  not  have  been  at  the  expense  of  protein  metab- 

1  Heineman:   "Pfliiger's  Archiv,"  1900,  Ixxxiii,  p.  476. 

2  Atwater  and  Benedict:  "Experiments  on  the  Metabolism  of  Matter  and 
Energy  in  the  Human  Body,"  1903,  U.  S.  Dept.  of  Agriculture,  Bulletin  136. 


320  SCIENCE   OF   NUTRITION 

olism;  but  it  is  also  plain  that  the  work  could  have  been 
derived  from  carbohydrate  combustion,  even  in  the  "fat" 
diet  of  Period  II. 

These  experiments,  however,  were  the  first  to  demonstrate 
exactly  that  mechanical  work  was  done  at  the  expense  of  a 
dynamic  equivalent  of  metabolism — a  splendid  confirmation 
of  the  law  of  the  conservation  of  energy. 

In  one  other  experiment  Atwater  and  Benedict  calculated 
for  J.  C.  W.  a  metabolism  amounting  to  9981  calories,  divided 
as  follows:  Protein,  478  calories;  fat,  7744  calories;  carbohy- 
drates, 1759.  The  man  worked  for  sixteen  hours  on  the 
bicycle.  The  work  done  measured  an  equivalent  of  1482 
calories;  the  body  heat  production  was  7382  calories,  both  of 
which  were  measured  in  the  Atwater  calorimeter,  and  the 
total  energy  loss  reached  9314  calories,1  a  height  of  metab- 
olism attained  also  by  Maine  lumbermen2  actively  employed 
(see  p.  348). 

Later  work  by  Benedict  and  Cathcart3  includes  an  ex- 
periment on  a  professional  bicycle  rider  who  rode  a  stationary 
bicycle  for  four  hours  and  twenty-two  minutes,  accomplishing 
208,000  kilogrammeters  of  work  during  this  period,  or  nearly  13 
kilogrammeters  per  second.  The  work  was  the  equivalent  of 
more  than  a  "century  run,"  or  over  100  miles  (161  kilometers). 
The  subject  rode  to  exhaustion.  When  lying  on  a  couch  before 
the  experiment  the  basal  metabolism  of  this  man  was  1.14 
calories  per  minute,  the  R.  Q.  was  0.85,  pulse  63,  and  respira- 
tion 20  per  minute.  The  basal  value  for  the  work  experiment 
was  ascertained  by  determining  the  heat  production  of  the 
man  sitting  on  the  bicycle  and  revolving  the  wheel  when  it 
offered  no  resistance. 


1  The  calories  calculated  from  the  metabolism  and  those  directly  measured 
by  the  calorimeter  did  not  exactly  agree  in  this  particular  instance — an  exception 
in  a  brilliant  series. 

2  Woods  and  Mansfield:   U.  S.  Dept.  of  Agriculture,  1904,  Bulletin  149. 

3  Benedict,  F.  G.,  and  Cathcart:  "Muscular  Work,"  Carnegie  Institution, 
1914,  Publication  187. 


INFLUENCE    OF    MECHANICAL    WORK    ON    METABOLISM     32 1 

The  following  table  presents  the  results: 

METABOLISM  DURING  A  "CENTURY  RUN"  ON  A  BICYCLE 

Subject,  M.  A.  M.;  Weight=65.9  Kilograms. 


Aver- 
age. 


0<  liters  per  minute 

R.Q 

Pulse-rate 

Respiration  rate 

Work    done    per    minute 

(calories) 

Mechanical  efficiency  (per 

cent.) 

Calories  per  minute 

Basal  value*  (calories) 


9 

9-45 

10.30 

11. 15 

12.00 

12-45 

A.  M. 

A.  M. 

A.  il. 

A.  M. 

NOON. 

P.  M. 

I.Q7 

i-95 

1-97 

i-95 

2.00 

I.9O 

O.9O 

0.91 

O.89 

0.89 

O.97 

O.88 

129 

128 

I36 

1.S6 

l60 

3° 

32 

30 

36 

36 

I.96 

1.96 

1.97 

1.94 

1.92 

i-73 

34-0 

34-4 

34-2 

34-3 

3i-4 

3°-4 

9.66 

9,S« 

9-65 

9-54 

10.01 

9.28 

(3-89) 

(3-»9) 

(3-89) 

(3-89) 

(3-89) 

0.91 

i-95 
9-75 


No  load  experiments,  without  motor. 


It  is  of  great  interest  that  the  respiratory  quotient  should 
have  remained  at  about  0.90  throughout  the  experiment, 
which  indicated  that  the  body's  glycogen  was  being  used  in 
goodly  measure  throughout  the  whole  period.  A  calculation 
shows  that  368  grams  of  glycogen  must  have  been  consumed 
during  the  time  of  the  ride.  The  average  respiratory  quotients 
of  thirty-four  days  of  experimentation  with  this  individual 
presents  the  following  results: 


R.Q. 


Rest. 
o.8S 


Work. 
0.88 


After  Work. 
0.78 


The  lower  respiratory  quotient  after  mechanical  work 
indicates  the  exhaustion  of  body  glycogen. 

The  production  of  600  calories  per  hour  is  probably  in  the 
neighborhood  of  the  highest  possible  maximum  of  human  phys- 
ical capacity  for  sustained  effort  (see  p.  431).  The  mechanical 
efficiency  of  33  per  cent,  is  the  same  as  that  previously  des- 
cribed by  the  Zuntz  school  for  raising  the  body  of  an  individual 
in  mountain  ascents.  The  leg  muscles  are,  therefore,  remark- 
ably efficient  machines. 


32  2  SCIENCE   OF   NUTRITION 

This  work  confirms  that  of  Johansson,1  that  the  subjective 
sense  of  strain  or  fatigue  has  no  influence  upon  metabolism. 

Benedict  and  Cathcart  further  report  a  considerable  in- 
crease in  the  basal  metabolism  obtained  lying  down  after 
severe  muscular  work,  the  stimulating  influence  persisting  for 
five  or  six  hours.  For  example,  a  man  whose  basal  metabolism 
was  determined  as  1.15  calories  per  minute  rode  a  bicycle 
seventy-four  minutes,  doing  work  which  was  the  equivalent  of 
2.06  calories  per  minute.  During  four  and  a  half  hours  of  sub- 
sequent rest  the  basal  metabolism  was  determined  eight  times, 
and  gave  values  between  1.35  and  1.33  calories  per  minute  in 
each  instance.  The  rate  of  the  pulse  fell  from  93  in  the  first 
observation  to  75  in  the  last,  that  of  the  respiration  from 
24  to  22. 

Mettenleiter2  states  that  after  hard  exercise  there  is  a  fall 
in  carbon  dioxid  tension  in  arterial  blood  lasting  several  days, 
due  to  a  long  continuing  slight  acidosis  (see  p.  421). 

The  stimulus  to  the  increased  metabolism  is  undoubtedly 
due  to  lactic  acid.  The  rise  in  metabolism  after  giving 
alanin,  which  is  convertible  into  lactic  acid,  is  sufficient  evi- 
dence that  lactic  acid  stimulates  metabolism  (see  p.  240). 

Barcroft3  climbed  a  straight  path  to  a  height  of  1000  feet 
(303  meters)  in  thirty  minutes,  a  performance  which  involved 
only  moderate  effort.  Observations  of  the  carbon  dioxid 
content  of  the  alveolar  air  and  the  hydrogen  ion  concentra- 
tion of  the  blood  gave  the  following  results: 

CO.  IN  „ 

Alveoli.  ph  °f  Blood- 

Mm. 

Normal 40  7.29 

After  ascent 35  7.09 

The  difference  in  acidosis  corresponds  to  an  addition  of 
0.023  per  cent,  of  lactic  acid  to  the  blood.     In  another  subject 

Johansson:  "Skan.  Archiv  fur  Physiologie,"  1901,  xi,  273;  Frumerie: 
Ibid.,  1913,  xxx,  409. 

2  Mettenleiter:   "Deutsches  Archiv  fur  klinische  Medizin,"  1915,  cxvii,  517. 

3  Barcroft:    "The  Respiratory  Function  of  the  Blood,"  1914,  p.  236. 


INFLUENCE    OF   MECHANICAL    WORK    ON   METABOLISM      323 

(Roberts)  who  made  the  same  ascent  the  amount  of  lactic  acid 
necessary  to  reduce  the  alkalinity  of  his  blood  to  the  level 
actually  found  was  estimated  at  0.029  per  cent.,  and  the  in- 
crease, as  determined  by  analysis  of  the  blood,  amounted  to 
0.032  per  cent.  Barcroft  gives  the  following  analysis  of  this 
state  of  affairs:  During  the  ascent  lactic  and  carbonic  acids, 
and  these  only,  were  added  to  the  blood.  On  account  of  the 
increased  hydrogen  ion  concentration,  the  hemoglobin  at  a 
given  pressure  takes  up  oxygen  less  readily  than  usual  and 
the  respiratory  center  is  stimulated.  The  increased  respira- 
tions cause  the  excessive  carbon  dioxid  produced  to  be  expired, 
and  not  only  the  excess  but  somewhat  more  than  this;  the 
carbonic  acid  pressure  in  the  alveolar  air  therefore  falls. 
Lactic  acid,  however,  is  not  got  rid  of  so  quickly  as  the  carbon 
dioxid,  and  is  retained.  The  increase  in  the  hydrogen  ion 
concentration  of  the  blood  causes  a  readier  dissociation  of  the 
oxyhemoglobin  contained  in  the  large  and  quickly  flowing 
volume  of  blood  which  passes  through  the  capillaries  of  the 
muscle.  At  the  same  time  the  increased  ventilation  of  the 
lungs  increases  the  oxygen  tension  in  the  alveoli,  and,  since  the 
absorption  of  oxygen  by  the  plasma  is  proportionate  to  the 
oxygen  pressure,  the  decreased  avidity  of  hemoglobin  for 
oxygen  caused  by  the  increased  hydrogen  ion  concentration  is 
compensated  for. 

The  formation  of  lactic  acid  may  be  attributed  to  a  local 
anemia  during  mechanical  work.     (See  Chapter  XV.) 

Brezina  and  Kolmer1  report  that  the  height  of  the  initial 
respiratory  quotients  obtained  during  periods  of  mechanical 
work  are  proportional  to  the  intensity  of  the  work  accom- 
plished. When  1.6  calories  represented  the  total  metabolism 
per  minute  the  R.  Q.  was  0.83,  and  when  the  metabolism  rose 
to  10  calories  the  R.  Q.  was  0.99.  Formation  of  acid,  with  the 
consequent  elimination  of  carbon  dioxid  from  the  blood  itself, 
in  part  explains  the  high  quotient  obtained.  Increased 
ventilation  and  carbohydrate  utilization  are  also  undoubtedly 

1  Brezina  and  Kolmer:   "Biochemische  Zeitschrift,"  1014,  lxv,  16. 


324  SCIENCE    OF   NUTRITION 

contributory.  An  increased  acid  formation  tends  to  cause  the 
conversion  of  liver  glycogen  into  sugar  (see  p.  421). 

Although  from  Zuntz's  work  it  seems  proved  that,  in 
furnishing  power  for  mechanical  work,  carbohydrates  and  fat 
are  replaceable  one  for  the  other  according  to  their  dynamic 
values,  there  is  a  well-founded  belief  that  work  may  be  ob- 
tained in  larger  quantity  from  an  individual  if  carbohydrates 
be  available. 

Schumburg1  finds  that  ingestion  of  carbohydrates  enables 
a  fatigued  muscle  to  contract  more  powerfully.  Hellsten2 
states  that  in  doing  mechanical  work  in  the  morning  before 
breakfast,  an  improved  capacity  occurs  thirty  to  forty  minutes 
after  ingesting  sugar. 

The  ready  exhaustion  of  diabetics  who  cannot  burn 
glucose  confirms  this  observation. 

Lee  and  Harrold3  have  found  evidences  of  great  fatigue  in 
the  excised  muscles  of  a  cat  from  which  the  readily  com- 
bustible sugar  had  been  removed  by  rendering  the  cat  diabetic 
with  phlorhizin.  Another  cat  similarly  treated,  the  body  of 
which,  however,  had  been  flooded  with  sugar  by  ingestion 
before  the  animal  was  killed,  showed  a  much  larger  capacity 
for  muscular  contraction. 

The  writer4  while  injecting  phloretin  solutions  into  the 
jugular  vein  of  fasting  rabbits,  diabetic  through  phlorhizin, 
noticed  that  seven  out  of  eight  rabbits  had  convulsions,  while 
normal  rabbits  were  not  so  affected.  Four  died  and  three  lost 
motor  control  of  the  muscles  of  their  limbs.  In  these  three 
there  was  an  increased  glucose  elimination  in  the  urine  on 
account  of  the  passage  of  the  glycogen  content  of  the  organs 
into  the  blood,  which  glycogen  would  normally  be  immediately 
available  for  muscular  activity  (p.  107).  The  animals  which 
survived  the  convulsions  regained  control  of   their  muscles 

1  Schumburg:   "Archiv  fur  Physiol ogie,"  1896,  p.  537. 

2  Hellsten:   "Skan.  Archiv  fur  Physiologie,"  1904,  xvi,  139. 

3  Lee  and  Harrold:  Proceedings  of  the  American  Physiological  Society, 
"American  Journal  of  Physiology,"  1900,  iv,  p.  ix. 

4Lusk:   "Zeitschrift  fur  Biologie,"  1898,  xxxvi,  109. 


INFLUENCE    OF    MECHANICAL    WORK    ON    METABOLISM      325 

in  two  to  four  hours.  This  indicates  a  slow  preparation 
from  fat  of  materials  available  for  the  production  of  muscle 
work. 

Schumburg1  finds  that  coffee  and  tea  have  no  recuperative 
power  over  the  muscles  of  a  fatigued  organism  except  when 
taken  with  other  foods,  and  that  the  stimulating  action  of  al- 
cohol is  only  temporary.  Hellsten,2  exercising  before  break- 
fast, finds  that  the  effect  of  taking  tea  is  almost  negligible,  and 
that  the  effect  of  alcohol  is  at  first  to  increase  the  muscle  power, 
but  that  after  twelve  to  forty  minutes  there  is  a  decrease  in 
power  which  lasts  for  two  hours.  No  such  depression  occurs 
after  taking  sugar.  It  is  obvious  that  alcohol  is  not  beneficial 
when  muscular  work  is  to  be  accomplished. 

The  carbon  dioxid  produced  as  a  result  of  mechanical  work 
is  quickly  eliminated  through  the  lungs.  Higley  and  Bowen3 
find  that  the  increased  elimination  begins  twenty  seconds  after 
the  commencement  of  bicycle  riding  and  reaches  its  maximum 
in  about  two  minutes.  At  this  point  it  remains  constant  from 
minute  to  minute,  provided  the  same  amount  of  work  is  done. 
This  principle  has  been  frequently  demonstrated  by  Zuntz  and 
his  pupils.  It  is  evident,  however,  that  the  quantity  of  carbon 
dioxid  excretion  for  the  unit  of  work  accomplished  will  be  less 
during  starvation  and  on  a  fat  diet  than  when  carbohydrates 
are  ingested,  by  reason  of  the  higher  heat  value  of  fat  carbon.4 

Johansson  and  Koraen5  have  caused  a  man  to  raise  a 
weight  of  21.7  kilograms  |  meter  high,  each  movement  last- 
ing one  second,  and  there  being  in  different  experiments  300, 
600,  720,  and  900  movements  per  hour.  In  the  trained  indi- 
vidual the  quantity  of  increase  in  the  carbon  dioxid  expired 
was  exactly  proportional  to  the  number  of  the  movements  in 
the  unit  of  time.  The  experiments  were  performed  when  food 
was  absent  from  the  intestines. 

Schumburg:    Loc.  cit. 

2  Hellsten:   Loc.  cit. 

3  Higley  and  Bowen:   "American  Journal  of  Physiology,"  1904,  xii,  335. 

4  Johansson  and  Koraen:  "Skan.  Archiv  fur  Physiologie,"  1902,  xiii,  251. 

5  Johansson  and  Koraen:  Ibid.,  1903,  xiv,  60. 


326  SCIENCE   OF   NUTRITION 

It  has  already  been  shown  (see  p.  318)  that  25  per  cent. 
of  the  total  energy  of  the  increase  above  the  resting  metab- 
olism as  caused  by  work  is  converted  into  mechanical  energy 
by  a  person  turning  the  wheel  of  an  ergostat  with  his  arms. 

Katzenstein1  has  shown  a  still  more  economical  utilization 
of  the  fuel  when  the  work  accomplished  is  climbing,  about  35 
per  Cent,  of  the  total  increase  in  metabolism  being  then  con- 
verted into  mechanical  effect.  Walking,  the  commonest  mus- 
cular exercise,  is  accomplished  with  the  greatest  mechanical 
efficiency. 

A  great  many  interesting  details  have  been  worked  out  in 
Zuntz's  laboratory  by  his  pupils.  The  following  epitome  of 
long  investigations  shows  the  comparative  energy  equivalents 
necessary  for  dog,  horse,  and  man  to  move  1  kilogram  of 
body  weight  1  meter  with  a  given  rapidity  along  a  horizontal 
plane  or  to  lift  1  kilogram  of  body  weight  1  meter  high.2 
The  experiments  were  made  by  placing  the  individual  on  a 
moving  platform,  the  speed  and  incline  of  which  could  be 
varied. 

A  study  of  the  table  on  p.  327  will  show  that  it  requires 
much  less  energy  for  a  horse  to  move  1  kilogram  of  his  weight 
1  meter  horizontally  than  for  a  dog  to  do  the  same  at  the 
same  velocity.  It  also  appears  that  a  man  of  small  weight 
requires  more  energy  to  a  unit  of  substance  than  a  man  of 
large  size.  This  rule  has  been  confirmed  in  dogs  by  SlowtzofT,3 
who  shows  that  energy  amounting  to  0.529  kilogramme ter 
is  required  for  1  meter  horizontal  motion  by  a  dog  weighing 
37  kilograms,  and  1.138  kilogrammeters  by  a  dog  weighing 
5.5  kilograms.  SlowtzofT  does  not  find  that  this  variation  is 
proportional  to  the  skin  area  of  the  animal. 

The  table  also  shows  that  there  is  little  variation  in  the  dog, 
horse,  and  man  in  the  amount  of  energy  necessary  to  raise  1 
kilogram  of  body  substance  1  meter  high: 

1  Katzenstein:   "Pfliiger's  Archiv,"  1891,  xlix,  379. 

2  Frentzel  and  Reach:   Ibid.,  1901,  lxxxiii,  494. 

3  Slowtzoff :  Ibid.,  1903,  xcv,  190. 


INFLUENCE    OF   MECHANICAL    WORK    ON   METABOLISM      327 


ENERGY    REQUIREMENTS    OF    DIFFERENT    ANIMALS    IN    PER- 
FORMANCE OF  THE  SAME  AMOUNT  OF  MECHANICAL  WORK 


Animal. 


Dog.. 
Dog.. 
Horse 

Man. 


Man. 

F. 
Normal  locomotion 

F. 
Slow  locomotion. . . 

R. 
Normal 

R. 
Slow 


Energy  Requirement 

in  Kilogrammeters. 

Velocity  in 
Meters 
per  Min- 
ute of 

Weight. 

For  Moving 

For  Raising 

Horizontally 

1  Kg. 

1  Kg. 

1  Meter 

1  Meter. 

High. 

26.9 
26.9 

0.495 
O.501 

2.954 
3-259 

J    78.57 

456.8 

O.137 

2.QI2 

78.57 

55-5 

0-334 

2.857 

74.48 

72.9 

O.217 

3.190 

71.32 

67.9 

0.2II 

3.140 

71.46 

80.0 

O.288 

3-563 

51-23 

88.2 

O.263 

3-555 

42.34 

72.6 

O.284 

2.913 

62.04 

81.1 

O.23I 

2.921 

60.90 

80.0 

O.244 

2.729 

56.54 

86.5 

O.219 

1-   2.746 

66.94 

86.5 

0-233 

J 

35-92 

65.S 

O.23O 

!•   2.846 

63-95 

65.8 

O.25I 

J 

34.58 

Incline  of 
Road  in  Per 
Cent.  Dur- 
ing Climb- 
ing Ex- 
periment. 


17.2 
10.3 

9-6-13-3 

6-5 
30.7-62. 

■23-30.5 


23-3 


It  is  possible  to  calculate  the  food  ration  for  a  march  if  the 
figures  given  in  the  table  be  employed.  If  it  be  assumed  that 
a  man  weighing  70  kilograms  travels  74.4  meters  a  minute,  he 
wrill  accomplish  4.46  kilometers  or  2.7  miles  per  hour.  If  it 
requires  the  energy  equivalent  of  0.217  kilogrammeter  to 
move  1  kilogram  of  his  weight  1  meter,  it  will  require  67,747 
kilogrammeters  (0.217  X  70  X  4460)  to  move  him  4.46  kilo- 
meters— 67,747  kilogrammeters  being  equivalent  to  159.205 
calories.  This  is  the  equivalent  of  17.1  grams  of  fat,  which 
may  be  added  to  the  maintenance  resting  dietary  requirement 
to  supply  the  energy  necessary  for  an  hour's  quiet  walk  on  a 
level  road.  If  the  road  be  inclined  so  that  the  man  raises 
himself  500  meters  during  the  hour's  walk,  the  metabolism  will 
be  still  further  increased.  The  work  of  ascent  will  be  his 
wreight  multiplied  by  the  height  of  his  climb,  or  35,000  kilo- 
grammeters.    The  expenditure  of  energy  by  the  body  in  order 


328 


SCIENCE   OF   NUTRITION 


to  accomplish  this  work  is  threefold  the  work  done,  or  105,000 
kilogrammeters,  which  equals  246.75  calories,  or  26.5  grams  of 
fat.  The  hour's  walk  in  this  case  would  require  the  produc- 
tion of  an  energy  equivalent,  above  the  resting  metabolism, 
amounting  to  that  contained  in  43.6  grams  of  fat — that  is, 
1 7. 1  grams  for  a  forward  locomotion  of  4.46  kilometers  and 
26.5  grams  to  lift  the  body  to  an  altitude  of  500  meters. 

In  the  last-mentioned  table  it  is  seen  that  there  is  an  in- 
crease in  the  metabolism  for  a  unit  of  horizontal  motion  when 
the  progress  of  the  individual  is  very  slow.  This  is  explained 
by  the  fact  that  speed  of  progress  was  half  the  normal,  was 
unusual,  and  forced. 

Later  work  has  confirmed  the  results  above  enumerated. 
Thus,  Brezina  and  Reichel1  find  that  a  man  walking  on  a 
horizontal  plane  at  a  rate  not  exceeding  80  meters  in  one 
minute  (3  miles  per  hour),  a  rate  which  they  denote  as  the 
maximal  economic  velocity,  requires  0.5  calorie  of  energy 
(=  0.213  kilogrammeter  of  work)  to  move  1  kilogram  of 
weight  1  meter,  and  this  rule  also  applies  to  Weights  carried 
up  to  about  20  kilograms.  This  load  is  about  that  carried  by 
a  soldier.  With  weights  heavier  than  this  there  is  a  slight 
increase  in  the  quantity  of  energy  required  when  the  individual 
labors  within  the  limits  of  the  maximal  economic  velocity. 
When,  however,  this  velocity  is  exceeded  the  expenditure  of 
energy  for  more  rapid  walking  increases  rapidly,  and  with 
especial  sharpness  when  heavy  loads  are  carried.  A  part  of 
the  figures  is  given  in  the  following  table: 

THE  INFLUENCE  OF  VELOCITY  AND  OF  LOAD  IN  HORIZONTAL 
WALKING  UPON  THE  AMOUNT  OF  ENERGY  IN  GRAM- 
CALORIES  NECESSARY  TO  MOVE  1  KG.  OF  WEIGHT  THROUGH 
1    METER   OF   DISTANCE 


Distance  in 

Meters  per 

Minute. 

Miles 

PER 

Hour. 

Load 
Equals 
3  Kg. 

Load 
Equals 
14  Kg. 

Load 

Equals 
24  Kg. 

Load 
Equals 
36  Kg. 

Load 
Equals 
46  Kg. 

Load 
Equals 
56  Kg. 

44.7-  49.7 
68.9-   73.3 
89.9-  92.0 

111.4-118.1 

141. 0 

1.8 

2.7 
3-4 
4-3 
5-3 

0.48 
0.60 

o.57 
0.77 

o.93 

0.48 
0.47 
0.62 
0.93 

0-57 
°-52 
°-59 
0.91 

o.59 
0-53 
0.64 
0.91 

0.58 
0.56 
0.81 

Q-59 
o.59 
0.77 

brezina  and  Reichel:    "Biochemische  Zeitschrift,"  1914,  lxili,  170. 


INFLUENCE    OF    MECHANICAL   WORK    ON   METABOLISM     329 

Benedict  and  Murschhauser1  have  arrived  at  essentially  the 
same  results  as  those  given  above  as  regards  the  energy 
requirement  involved  in  horizontal  walking,  and  they  further 
note  that  running  at  the  rate  of  about  5.3  miles  per  hour  is 
accomplished  more  economically  than  walking  at  the  same 
rate.     Their  results  may  be  summarized  as  follows: 

Gram-Calories 
Distance  in  Meters  for  Horizontal 

per  Minute.  Kilogram  i  Meter. 

'(   7i-5  0.403 

Walking -j  106.3  0.585 

[144.1  0.032 

Running M7-5  0.806 

The  total  heat  produced  when  walking  at  the  higher  speed 
was  about  600  calories  per  hour,  or  about  that  of  the  same 
individual  (M.  A.  M.)  when  he  rode  a  bicycle,  as  already 
described  (p.  321).  At  the  lower  speed  it  was  found  that 
the  process  of  walking  involved  a  total  lifting  of  the  body 
weight  from  the  ground,  amounting  approximately  to  a  height 
of  4  meters  per  minute.  The  energy  necessary  to  do  this 
would  account  for  25  per  cent,  of  the  total  energy  utilized  in 
the  muscular  complex  thrown  into  action  for  the  purpose  of 
forward  progression. 

The  generalization  of  Brezina  and  Reichel  is  that  within 
the  limit  of  economic  maximal  velocity  the  energy  requirement 
of  the  organism  approximates  a  constant  minimum  value, 
which  is  0.5  gram-calorie  for  the  forward  movement  of  1 
kilogram  of  weight  1  meter  horizontally.  With  each  meter 
of  velocity  above  80  meters  per  minute  the  requirement  of 
energy  increases  1  per  cent,  of  the  initial  minimal  value. 
When  medium  loads  (20  kg.)  are  carried  the  metabolism  in- 
creases 2  per  cent.,  and  with  heavy  loads  3  per  cent.,  of  the 
minimal  value,  per  each  added  meter  of  velocity  above  80 
meters  per  minute. 

The  Pale  is  that  the  metabolism  increases  with  speed  in 

1  Benedict,  F.  G.,  and  Murschhauser:  "Energy  Transformations  During 
Horizontal  Walking,"  Carnegie  Institution,  Publication  231,  1915. 


330  SCIENCE    OF   NUTRITION 

horses  (1.03  per  cent,  per  meter  increase  above  78  meters  per 
minute),  but  this  is  not  seen  in  dogs.1 

Brezina  and  Reichel2  continued  their  researches  by  de- 
termining the  effect  of  the  gradient  of  the  pathway  upon  the 
metabolism  of  man  when  walking  and  carrying  different 
loads.  It  was  found  that  the  maximal  work  of  lifting  the  body 
with  its  load  was  accomplished  at  a  minimal  expenditure  of 
energy  when  the  incline  was  20  per  cent,  and  the  weight  of  the 
load  19  kilograms.  However,  when  walking  on  inclines 
with  gradients  of  10  or  40  per  cent.,  the  energy  figures  were 
only  slightly  above  the  minimal  values  and  the  load  also  made 
no  essential  difference.  The  authors  found  that  to  raise  1 
kilogram  of  body  substance  plus  the  load  carried,  required 
between  9  and  10  calories  of  energy  of  metabolism.  This 
represents  the  conversion  of  about  25  per  cent,  of  the  energy 
of  metabolism  into  mechanical  work.  Weights  between  3  and 
56  kilograms  were  raised  at  expenditures  of  energy  directly 
proportional  to  the  work  accomplished. 

Katzenstein3  finds  that  the  metabolism  during  the  descent 
of  a  mountain  is  less  by  10  per  cent,  than  the  increase  caused 
by  walking  on  a  level  surface.  The  muscles  which  act  to 
inhibit  a  too  rapid  descent  are  not  required  to  be  so  act- 
ive as  those  which  give  forward  impetus  to  the  body  on  a 
level  road. 

This  idea  has  been  still  further  investigated  by  moun- 
taineers,4 who  compared  the  actual  heat  production  with 
the  energy  of  metabolism  during  one  minute  for  horizontal 
motion  and  for  ascent  and  descent  of  a  mountain  path  which 
had  a  25  per  cent,  incline.     The  results  were  as  follows: 

Ascent,  28.8  3    Horizontal,  Descent, 

Meters.  100  Meters.        76  Meters. 

Calories  of  energy  of  metabolism 69.3  67.8  40.8 

Calories  of  heat  liberated 46.9  67.8  85.5 

1  Zuntz:   "Pfliiger's  Archiv,"  1003,  xcv,  192. 

2  Brezina  and  Reichel:    "Biochemische  Zeitschrift,"  1914,  lxv,  35. 

3  Katzenstein:    Loc.  cit.,  p.  376. 

4  Zuntz,  Loewy,  Miiller,  and  Caspari:  "Hohenklima  und  Bergwanderungen 
in  ihrer  Wirkung  auf  den  Menschen,"  1906. 


INFLUENCE   OF   MECHANICAL  WORK   ON   METABOLISM     33 1 

The  smallest  liberation  of  heat  occurred  during  the  ascent 
of  the  mountain  at  the  time  when  the  energy  of  metabolism 
was  being  converted  into  energy  of  position. 

The  largest  heat  production  occurred  during  the  descent  of 
the  mountain.  The  metabolism  was  the  least,  but  energy  of 
position  was  converted  into  heat  through  the  vibration  of  the 
body  at  each  footfall. 

Zuntz  and  Schumburg1  find  an  increase  in  the  metabolism 
of  a  marching  soldier  if  the  knapsack  be  badly  placed,  or  if 
the  body  be  sore  and  weary. 

Lavonius2  finds  the  maximum  amount  of  work  attainable 
by  a  trained  wrestler  of  great  reputation  to  be  the  equivalent 
of  t,o  kilogrammeters  per  second. 

Details  of  the  effect  of  position  upon  the  metabolism  of 
individuals  have  been  repeatedly  published  by  Benedict  and 
his  pupils.  Perhaps  the  most  interesting  of  these  studies  may 
be  taken  from  the  work  of  Benedict  and  Murschhauser3  upon 
the  basal  metabolism  of  the  professional  bicycle  rider,  M.  A.  M. 
The  results  may  thus  be  summarized: 


Calories  per 
Position.  Minute. 


Lying  (basal  metabolism) 1 

Sitting : 1 

Standing,  relaxed 1 

Standing,  hand  on  staff 1 

Standing,  leaning  on  support 1 

Standing,  "attention" 1 

Standing,  swinging  arms* 3 

*  As  in  rapid  walking. 


Pulse-rate. 


14 

19  61 

25  80 

26  80 
18  78 
3°  73 
13 


A  subject  of  very  great  interest  is  the  result  of  training.  It 
is  well  known  that  if  a  cobbler,  for  example,  be  removed  from 
his  trade  and  be  compelled  to  climb  a  mountain,  he  will  at  first 
be  of  little  use  as  compared  with  a  Swiss  guide.  But  after  con- 
tinued practice  the  blood-vessels  dilate  at  once  in  response  to 
the  needs  of  the  muscles  and  the  heart  expends  less  energy; 
unnecessary  motions  with  the  arms  and  legs  are  diminished  in 

1  Zuntz  and  Schumburg:  "Studien  zu  einer  Physiologie  des  Marsches," 
Berlin,  iqoi. 

2  Lavonius:    "Skan.  Archiv  fur  Physiologie,"  1905,  xvii,  196. 

3  Benedict  and  Murschhauser:    Loc.  cit. 


332 


SCIENCE    OF   NUTRITION 


number;  the  strain  for  the  accomplishment  of  a  given  piece 
of  work  diminishes;  the  thorax  enlarges  to  promote  readier 
respiration;  the  man  becomes  "trained,"  and  there  is  a  les- 
sened metabolism  for  the  fulfilment  of  a  definite  amount  of 
work. 

The  experimental  measurements  of  the  efficacy  of  the 
working  organism  as  described  above  were  made  on  well- 
trained  men,  a  difference  on  account  of  training  having  been 
early  recognized  by  Zuntz. 

Biirgi1  made  some  investigations  upon  an  individual  before 
and  after  training  for  mountain  climbing.  The  ascents  were 
made  at  different  altitudes  on  the  roadbed  of  mountain  rail- 
ways, and  the  carbon  dioxid  elimination  was  measured.  The 
results  are  shown  in  the  following  table : 

EFFECT  OF  TRAINING   ON  METABOLISM 


Place. 

Altitude  in 
Meters. 

Incline  of 
Road  in  per 

CENT. 

CO2  Excretion  per  Kgm.  of 
Work. 

Untrained. 

Trained. 

Brienz 

Gornergrat 

Brienz 

Gornergrat 

620 
2987 

690 
3021 

17.29 

19-3 
I9.O 

19-3 

2.430 
2. 711 
2.251 
2-445 

2.103 
2.268 
2.063 
2. 117 

It  is  evident  from  this  that  a  trained  mountaineer  accom- 
plishes his  work  at  the  expense  of  less  metabolism  than  does  the 
untrained.  Also  that  at  a  moderately  high  altitude  (3000 
meters  =  522  mm.  of  mercury,  barometric  pressure)  the 
trained  organism  is  as  efficient  for  mechanical  work  as  at  the 
sea-level,  whereas  the  untrained  man  required  a  much  greater 
metabolism  to  accomplish  a  unit  of  work  at  the  higher  altitude 
than  at  the  lower. 

Another  fact  of  importance  is  that  the  effect  of  training 
especially  affects  the  muscles  involved  in  the  particular  move- 
ment, and  not  those  which  do  not  contract.     Thus  Zuntz2 

1  Biirgi:    "Archiv  fur  Physiologie,"  1900,  p.  509. 

2  Zuntz:   "Pfliiger's  Archiv,"  1903,  xcv,  200. 


INFLUENCE    OF   MECHANICAL   WORK   ON   METABOLISM     333 

found  that  a  dog  trained  for  horizontal  motion  on  a  level  street 
required  1179  small  calories  to  move  1  kilogram  body  weight 
1000  meters  and  7.668  small  calories  to  raise  1  kilogram  body 
weight  1  meter  high.  The  dog  was  then  gradually  trained  to 
ascend  an  incline.  After  two  years  he  required  only  5.868 
small  calories  to  lift  1  kilogram  1  meter,  but  he  required 
1343  small  calories  per  kilogram  for  horizontal  locomotion 
through  1000  meters.  Therefore  the  specifically  trained 
muscles  work  more  economically  than  those  which  are  at  the 
time  but  little  used. 

A  man  trained  for  mountaineering  will  often  find  himself 
uncomfortable  when  walking  on  a  level  road.  The  moun- 
taineer will  not  find  the  bicycle  an  easy  means  of  locomotion,1 
nor  will  the  bicylist  unscathed  essay  the  mountain. 

A  benefit  derived  from  riding  a  horse  is  the  shaking  of  the 
internal  organs,  which  is  also  achieved  by  descending  a  steep 
pathway.  This  may  be  beneficial  to  the  life  processes  in  such 
a  comparatively  immobile  organ  as  the  liver  for  example.  It 
also  appears  to  promote  a  freer  evacuation  of  the  bowels. 

In  swimming  there  is  considerable  respiration  gymnastics.2 
The  water  pressure  upon  the  thorax  is  the  equivalent  of  the 
weight  of  an  8-kilogram  sand-bag,  which  the  swimmer  seeks  to 
counterbalance  by  increasing  the  pressure  in  his  lungs  through 
puffing  with  his  lips.  By  turning  over  on  the  back  the  swim- 
mer removes  this  respiratory  influence.  Cold  water  stimu- 
lates metabolism  (p.  144),  but  the  effect  of  the  salt  in  ordinary 
sea  water  is  certainly  negligible. 

There  can  be  little  doubt  that  exercise,  especially  in  the 
open  air,  strengthens  the  organism  and  therefore  tends  to 
prolong  life.  Sometimes  muscular  exercise  is  mistakenly 
considered  as  favoring  intellectual  activity.  Yet  college 
presidents  are  not  selected  from  the  ranks  of  prize-fighters. 

1  Concerning  energy  expended  in  bicycle  riding  see  Berg,  Du  Bois-Reymond, 
and  L.  Zuntz:     Archiv  fur  Physiologie,"  Supplement,  1904,  p.  20. 

2  R.  Du  Bois-Reymond:  Ibid.,  1905,  p.  253. 


CHAPTER  XII 

A  NORMAL  DIET 

The  principles  of  metabolism  have  been  sufficiently  ex- 
plained in  the  foregoing  chapters  to  make  it  possible  to  under- 
stand the  basis  of  a  diet  which  shall  be  physiologically  rational. 

It  has  been  seen  that  the  average  starvation  metabolism 
of  a  vigorous  man  at  light  work  and  weighing  70  kilograms 
approximates  2240  calories,  or  32  calories  per  kilogram.  It  is 
obvious  that  this  quantity  of  energy  must  be  contained  in 
the  daily  food,  and  a  little  more  to  counterbalance  the  "specific 
dynamic"  or  heat-increasing  power  of  the  food-stuffs,  if  the 
individual  is  to  be  maintained  in  calorific  equilibrium.  It  has 
been  seen  that  when  an  average  mixed  diet  is  ingested  the 
maintenance  requirement  is  between  11.1  and  14.4  per  cent, 
above  the  starvation  minimum  (p.  239).  This  would  amount 
to  from  2488  to  2562  calories,  or  from  35.5  to  36.6  calories  per 
kilogram  of  body  weight  in  the  case  of  the  individual  just 
referred  to. 

Rubner1  is  authority  for  the  following  table,  which  indicates 
the  energy  requirement  of  men  of  various  weights  while  doing 
light  work: 

Weight  Area  in  Calories  of  Calories 

in  Kg.  Sq.  M.  Metabolism.  per  Kg. 

80 2.283  2864  35-8 

70 2.088  2631  37.7 

60 1.885  2368  39.5 

50 1.670  2102  42.0 

40 1-438  1810  45.2 

Since  man  through  clothing  shuts  himself  off  from  the 
reflex  action  of  cold  on  the  skin,  the  greatest  factor  which 
tends  to  increase  his  metabolism  is  mechanical  work,  and  the 

1  Rubner:  von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1903,  Bd.  i, 
P-  153- 

334 


A   NORMAL  DIET  335 

total  amount  of  calories  required  is  here  dependent  on  the 
kind  and  the  amount  of  the  work  accomplished.  The  re- 
quirements in  this  regard  have  already  been  discussed. 

A  point  of  great  interest  is  that  of  the  proper  proportion  in 
which  the  individual  food-stuffs  should  be  put  together  in 
making  up  a  ration. 

Voit  defines  a  food  as  a  well-tasting  mixture  of  food-stuffs 
in  proper  quantity  and  in  such  a  proportion  as  will  least 
burden  the  organism.     What  is  the  proper  proportion? 

Voit1  gives  the  following  ration  for  the  use  of  an  average 
laborer,  such  as  a  soldier  in  a  garrison — that  is,  for  a  man  at 
work  from  eight  to  ten  hours  a  day:  Protein,  118  grams;  car- 
bohydrates, 500  grams;  fat,  56  grams.  This  diet  contains 
3055  calories. 

Such  a  ration  means  the  food  actually  ingested.  It  is  also 
assumed  that  the  food-stuffs  are  administered  in  a  digestible 
form,  and  are  therefore  completely  assimilable.  It  has  already 
been  pointed  out  in  the  Introductory  Chapter  that  the  feces 
contain  no  undigested  protein  when  good  food  is  given.  It 
is,  therefore,  fallacious  to  deduct  the  nitrogen  of  the  feces  from 
the  nitrogen  of  the  ingesta  in  order  to  determine  the  amount  of 
protein  assimilated.  Fecal  nitrogen  plus  urinary  nitrogen 
together  represent  the  waste  of  assimilable 'protein  nitrogen 
(see  p.  47). 

The  allowance  of  118  grams  of  protein  has  provoked  much 
discussion.  The  original  figures  were  obtained  by  Voit  by 
averaging  the  protein  metabolism  of  many  laboring  men. 
This  requirement  of  protein  was  therefore  obtained  by  the 
statistical  method,  which  simply  showed  what  the  average 
laborer  in  habit  consumed.  For  the  same  class  of  artisan  the 
diet  given  by  Rubner  calls  for  127  grams  of  protein;  by  At- 
water,  125  grams;  and  Lichtenfelt2  confirms  Voit's  average  as 
being  the  quantity  of  protein  taken  by  laborers  in  northern 
Italy. 

1  Voit:   "Physiologie  des  Stoffwechsels,"  1881,  p.  519. 

2  Lichtenfelt:   "Pfluger's  Archiv,"  1903,  xcix,  1. 


336  SCIENCE    OF   NUTRITION 

For  men  at  hard  labor,  such  as  soldiers  in  the  field,  even 
higher  quantities  of  protein  are  commended — by  Voit,  145 
grams;  by  Rubner,  165  grams;  by  Atwater,  150  grams.  These 
figures  again  are  based  on  statistics.  Woods  and  Mansfield1 
found  that  the  average  protein  in  the  ration  of  fifty  lumber- 
men is  164  grams. 

In  striking  contrast  to  this  Siven,2  at  the  age  of  thirty-one 
and  a  half  years  and  weighing  65  kilograms,  finds  he  can  main- 
tain himself  in  nitrogen  equilibrium  for  a  short  period  on  a  diet 
containing  between  4  and  5  grams  of  nitrogen,  or  25  to  31  grams 
of  protein.  In  fact,  in  one  experiment  the  food  contained  4 
grams  of  nitrogen,  of  which  2.4  grams  only  were  in  15.4  grams 
of  true  protein  and  the  balance  in  amino-acids  and  other  nitrog- 
enous non-protein  matter  of  vegetable  origin.  Here  nitrogen 
equilibrium  was  nearly  attained,  the  nitrogen  ingested  being 
4,  and  that  excreted  4.28  grams.  The  food  given,  which  was 
rich  in  carbohydrates,  contained  2717  calories,  or  43  calories 
per  kilogram,  and  the  total  metabolism,  as  estimated  by  res- 
piration experiments,  indicated  a  heat  production  of  2082  or 
32  calories  per  kilogram.  Here  was  practically  nitrogen 
equilibrium  maintained  at  the  minimum  level,  and  a  low 
total  metabolism  which  was  largely  at  the  expense  of  carbo- 
hydrates. 

It  will  be  recalled  that  the  quantity  of  nitrogen  in  the  urine 
in  the  average  fasting  man  who  has  been  previously  well  nour- 
ished is  10  grams,  a  minimum  which  is  reducible  only  by  carbo- 
hydrate ingestion. 

The  experiments  of  Siven  did  not  satisfy  people  that  a  low 
protein  metabolism  was  compatible  with  continued  health  and 
strength.  Munk3  and  Rosenheim4  both  found  that  dogs  given 
a  quantity  of  protein  sufficient  only  to  maintain  nitrogen 
equilibrium  gradually  lost  strength  and  became  afflicted  with 

1  Woods  and  Mansfield:  "Studies  of  the  Food  of  Maine  Lumbermen," 
U.  S.  Department  of  Agriculture,  1904,  Bulletin  149. 

2  Siven:   "Skan.  Archiv  fur  Physiologie,"  1901,  xi,  308. 

3  Munk:    "Archiv  fur  Physiologie,"  1891,  p.  338. 

4  Rosenheim:   Ibid.,  p.  341. 


A    NORMAL   DIET  337 

digestive  disturbances.  These  experiments  fortified  the  idea 
of  the  benefits  to  be  derived  from  a  diet  containing  more 
protein  than  was  necessary  for  the  maintenance  of  nitrogen 
equilibrium — a  luxus  consumption.  Rubner  declared  that  a 
large  protein  allowance  is  the  right  of  civilized  man. 

The  tradition  that  a  continued  liberal  allowance  of  protein 
in  a  diet  is  a  prerequisite  for  the  maintenance  of  bodily  vigor 
has  been  dispelled  by  Chittenden1  and  his  co-workers,  of  whom 
Mendel  is  the  most  prominent. 

Professor  Chittenden  had  suffered  from  persistent  rheuma- 
tism of  the  knee-joint,  and  determined  on  a  course  of  dieting 
which  should  largely  reduce  the  protein  and  the  calorific  intake. 
The  rheumatic  trouble  disappeared,  and  minor  troubles,  such 
as  "sick  headaches"  and  "bilious  attacks,"  no  longer  recurred 
periodically  as  before.  "There  was  a  greater  appreciation  of 
such  food  as  was  eaten;  a  keener  appetite  and  more  acute  taste 
seemed  to  be  developed,  with  a  more  thorough  liking  for  simple 
foods."  During  the  first  eight  months  of  the  dieting  there 
was  a  loss  of  8  kilograms  of  body  weight.  Thereafter  for  nine 
months  the  body  weight  remained  stationary.  "Two  months 
of  the  time  were  spent  at  an  inland  fishing  resort,  and  during  a 
part  of  this  time  a  guide  was  dispensed  with  and  the  boat  rowed 
by  the  writer  frequently  6  to  10  miles  in  a  forenoon,  some- 
times against  head  winds  (without  breakfast) ,  and  with  much 
greater  freedom  from  fatigue  and  muscular  soreness  than  in 
previous  years  on  a  fuller  dietary." 

During  the  period  of  nine  months  the  nitrogen  of  the  urine 
was  determined  daily.  The  average  was  5.69  grams.  During 
the  last  two  months  and  a  half  the  average  elimination  was 
5.40  grams  for  a  body  weight  of  57.5  kilograms.  Experiments 
showed  that  about  1  gram  of  nitrogen  was  eliminated  in  the 
feces  and  that  nitrogen  equilibrium  could  be  maintained  with 
dietaries  of  low  calorific  values  (1613  and  1549  calories  =  28 
and  27  calories  per  kilogram)  containing  6.40  and  5.86  grams  of 
nitrogen.     These  figures  correspond  to  diets  containing  40.0  to 

1  Chittenden:   " Physiological  Economy  in  Nutrition,"  1904. 


33&  SCIENCE    OF   NUTRITION 

36.6  grams  of  protein  instead  of  the  118  grams  honored  by 
habit  and  tradition.  Professor  Chittenden  proclaimed  such  a 
diet  as  of  the  highest  importance  to  health. 

The  case  of  Chittenden  recalls  a  note  from  an  early  con- 
vert to  the  "Graham  system"  of  vegetarianism.  Sylvester 
Graham,  in  1829,  began  the  advocacy  of  moderation  in  the  use 
of  a  diet  consisting  of  vegetables,  Graham  bread  (made  of 
unbolted  flour),  fruits,  nuts,  salt,  and  pure  water,  and  exclud- 
ing meat,  sauces,  salads,  tea,  coffee,  alcohol,  pepper,  and  mus- 
tard. The  letter  reads  as  follows:1  "The  first  three  months  of 
my  experiment  on  the  Graham  system  was  attended  by  a 
loss  of  20  to  30  pounds  of  flesh.  Some  of  my  neighbors 
expostulated  with  me — told  me  I  should  destroy  myself  by 
starvation,  and  it  was  even  reported  in  a  neighboring  town 
that  I  had  actually  died  from  that  cause.  But  my  appetite  was 
increasingly  good  and  my  health  was  increasing,  and  in  a  short 
time  my  headaches,  colds,  costiveness,  and  rheumatism  left 
me  entirely,  together  with  my  hypochondriacal  and  gloomy 
state  of  mind,  and  have  not  returned  since,  notwithstanding 
I  have  been  as  much  exposed  to  wet  and  cold  as  at  any  period 
of  my  life." 

Chittenden's  experiments  were  not  confined  to  an  indi- 
vidual nor  to  a  single  group  of  individuals.  Other  experi- 
ments were  made  on  professional  men,  on  student  athletes  in 
training,  and  on  soldiers  under  military  regime.  The  daily 
nitrogen  in  the  urine  in  periods  extending  from  five  to  nine 
months  averaged  as  shown  in  the  table  on  p.  339  in  the  indi- 
viduals belonging  to  the  three  groups. 

At  convenient  periods  during  the  experiments  it  was  deter- 
mined that  the  body  was  being  maintained  in  nitrogenous 
equilibrium  on  the  diet  which  gave  rise  to  the  stated  amounts 
of  urinary  nitrogen  (see  p.  279). 

The  professional  group  alleged  a  greater  keenness  for  its 
work,  the  athletic  group  won  championships  in  games,  and  the 

1  Charles  Clapp:  "The  Graham  Journal  of  Health  and  Longevity,"  Boston, 
1837,  i,  57- 


A    NORMAL   DIET 


339 


soldiers  maintained  perfect  health  and  strength,  many  profess- 
ing repugnance  to  meat  when  they  were  allowed  it  after  five 
months  of  practical  abstinence. 


Professors  and  Teachers. 


Weight  in  Kg. 


57-° 
70.0 
65.0 
65.0 
61.5 


Nin 
Urine  in  G. 


5-69 
6-53 
7-43 
8.99 
8.58 


University  Athletes. 


Weight  in  K,2 


71.0 
61.0 
78.O 
83.O 
62.0 
56.O 
73-o 
75-o 


Nin 
Urine  in  G. 


9-37 

10.41 

8.88 

9.04 

7-47 

7-58 

10.09 

11.06 


United  States  Soldiers. 


Weight  in  Kg. 


62 

59 
60 

58 
60 

53 
7i 
72 
62 
59 
55 
65 
57 


Nin 
Urine  in  G. 


7.42 

7-03 
7.26 
S.17 
8-39 
7-13 
8.91 
7.84 
8.05 
7-38 
8.25 
8.08 
8.6l 


Although  it  is  possible  that  the  alleged  improved  mental 
condition1  may  have  been- due  to  suggestion  (p.  486),  still  the 
fact  remains  that  it  has  been  proved  by  Chittenden's  work 
that  the  allowance  of  protein  necessary  for  continued  health 
and  strength  may  be  reduced  during  many  months  to  half  or 
less  of  what  the  habit  of  the  appetite  suggests. 

It  remains  to  be  seen  whether  this  quantity  of  protein  in 
the  ration,  which  is  not  greater  than  the  body  would  metab- 
olize in  starvation,  is  advisable  as  a  program  for  the  whole  of 
one's  adult  life. 

The  foods  with  the  strongest  flavors  are  meats,  which  there- 
fore add  relish  to  a  repast  and  stimulate  the  digestive  secre- 
tions. 

Chittenden  believes  that  the  large  quantity  of  protein  in 

an  ordinary  diet  is  due  to  self-indulgence.    He  protests  against 

such  indulgence,  and  thinks  that  a  needless  strain  is  thereby 

imposed  upon  the  liver,  the  kidneys,  and  other  organs  con- 

1  Chittenden:   Loc.  cit.,  p.  51. 


340  SCIENCE    OF   NUTRITION 

cerned  in  the  transformation  and  elimination  of  the  end- 
products  of  protein  metabolism. 

Another  advocate  of  a  low  protein  dietary  has  arisen  in 
the  person  of  Hindhede,1  who  advocates  as  ideal  a  diet  consist- 
ing of  bread,  potatoes,  and  fruit,  together  with  a  small  quantity 
of  milk  when  this  latter  is  obtainable.  It  is  avowedly  a  "back- 
to-the-farm"  dietary.  Splendid  health,  both  of  body  and 
mind,  and  the  peasants'  comparative  immunity  to  indigestion, 
kidney  and  liver  disease,  to  diabetes,  as  well  as  an  absolute 
immunity  to  gout,  is  the  alluring  prospect  held  out  by  the 
following  dietary: 

Graham  bread 500  grams. 

Potatoes 1000      " 

Vegetable  margarin 150     " 

Apples 600      " 

Milk 500  c.c. 

Such  a  diet  gives  a  urine  which  dissolves  uric  acid  readily, 
the  addition  of  the  apples  appreciably  increasing  this  power. 
Hindhede  also  states  that  the  ingestion  of  5  kilograms  of 
tomatoes  with  600  grams  of  Graham  bread  and  150  grams  of 
margarin  daily  for  four  days  also  produces  a  urine  having  a 
good  solvent  power  over  uric  acid. 

In  analyzing  the  effect  of  the  factors  of  the  bread-potato- 
fruit  diet  Hindhede  found  that  an  exclusive  bread  diet  gave 
a  urine  which  exhibited  a  strong  tendency  to  deposit  uric  acid, 
and  notes  that  the  Russian  peasant,  who  works  fourteen  to 
sixteen  hours  daily  and  lives  almost  exclusively  upon  bread, 
frequently  has  gravel.  On  the  other  hand,  potatoes  when 
ingested  yield  a  urine  which  is  very  slightly  acid,  often  on 
the  border-line  of  alkalinity,  and  one  which  has  a  very  great 
solvent  power  over  uric  acid. 

It  is  a  curious  fact  that  the  potato,  long  proscribed  by 
many  physicians,  has  decided  therapeutic  value.  Some  one 
has  remarked,  "One  meets  the  potato  today  in  the  very  best 
circles." 

1  Hindhede:   "Skan.  Archiv  fur  Physiologie,"  191 2,  xxvii,  87. 


A   NORMAL  DIET  341 

Hindhede1  reports  the  following  results  upon  the  daily 
nitrogen  balance  after  giving  various  forms  of  bread  during 
periods  of  eight  days: 

In  Diet 
<-..™„,.  N  ±Nto  Body, 

Calories.  Grams.  Grams. 

Schwarzbrot      1000  g.  +  fat  120  g 3200  12.1  +0.3 

White  bread       900  g.  +  fat  120  g 3640  13.2  +0.6 

Rye  bread         1000  g.  +  fat  135  g 4000  12.8  —1.7 

Graham  bread  1000  g.  +  fat  140  g 38o°  I5-1  +°-4 

These  results  show  a  favorable  utilization  of  bread  protein. 

Concerning  the  utilization  of  potato  protein  Hindhede2 
reports  the  following  remarkable  experiment:  An  individual 
partook  of  a  diet  of  2  to  4  kilograms  of  potatoes  with  some 
margarin  daily  during  a  period  of  nearly  three  hundred  days. 
The  potatoes  were  well  boiled  in  water  and  the  water  in  which 
they  were  cooked  was  drunk  on  account  of  valued  salts  therein 
contained.  The  rule  was  to  eat  only  when  hungry.  Potatoes 
could  be  eaten  at  the  rate  of  100  grams  in  four  minutes. 
Stools  were  passed  once  every  three  or  four  days,  but  there  was 
no  constipation.  During  a  period  of  one  hundred  and  seventy- 
eight  days  6.05  grams  of  nitrogen  and  3725  calories  were  con- 
tained in  the  daily  diet,  and  there  occurred  an  average  daily 
loss  of  body  nitrogen  of  0.42  gram.  During  a  second  period 
of  ninety-five  days,  when  mechanical  work  was  performed, 
there  were  8.45  grams  of  nitrogen  and  4900  calories  in  the 
daily  diet  and  the  daily  loss  of  body  nitrogen  was  0.36  gram. 
During  these  ninety-five  days  the  food  supply  consisted  of 
350  kilograms  of  potatoes  and  22  kilograms  of  fat  taken  in 
the  form  of  margarin. 

Hindhede  states  that  he  "feels  weak"  after  taking  much 
meat. 

One  may  pass  now  to  the  other  side  of  the  story. 

Lichtenfelt3  shows  that  while  there  is  no  statistical 
difference  in  the  height  of  individuals  as  due  to  occupation, 
still  the  people  of  southern  Italy  are  not  so  large  nor  so  well 

1  Hindhede:    "Skan.  Archiv  fur  Physiologie,"  1913,  xxviii,  165. 

2  Hindhede:   Ibid.,  1913,  xxx,  97. 

3  Lichtenfelt:   "Pfluger's  Archiv,"  1905,  cvii,  57. 


342  SCIENCE    OF   NUTRITION 

developed  physically  as  their  fellows  of  northern  Italy.  He 
explains  this  stunted  growth  as  due  to  a  low  protein  and  cal- 
orific intake  in  the  food. 

Albertoni  and  Rossi1  describe  how  the  poorest  Italian 
peasants  in  southern  Italy  live  on  cornmeal,  green  stuffs,  and 
olive  oil,  and  have  done  so  for  generations.  There  is  no  milk, 
cheese,  or  eggs  in  their  dietary.  Meat  in  the  form  of  fat  pork 
is  taken  three  or  four  times  a  year.  Cornmeal  is  taken  as 
"polenta,"  or  is  mixed  with  beans  and  oil,  or  is  made  into  corn- 
bread.  Cabbage  or  the  leaves  of  beets  are  boiled  in  water 
and  then  eaten  with  oil  flavored  with  garlic  or  Spanish  pepper. 
The  average  elimination  of  urinary  nitrogen  of  13  persons  in 
three  families  when  taking  this  diet  was  for  men  8.1  and  for 
women  6.7  grams  of  nitrogen  daily.  The  investigators, 
furthermore,  considered  a  family  of  8  individuals  of  whom 
2  were  children.  The  annual  income  was  424  francs  or  $84. 
Of  this,  3  cents  per  day  per  adult  was  spent  for  food  and  the 
remaining  f  cent  daily  was  spent  for  other  purposes.  The 
addition  of  100  to  200  grams  of  meat  daily  to  the  diet  of  each 
of  these  individuals  increased  their  muscular  power,  and  the 
investigators  believed  that  such  an  addition  was  essential  to 
mental  health  as  well. 

The  position  of  the  food  extremists  was  powerfully  at- 
tacked by  Rubner,2  whose  general  tone  was  in  advocacy  of 
variety  in  the  dietary  of  man  in  accordance  with  the  then 
prevailing  habits  and  certainly  without  attempting  to  conform 
to  a  protein  minimum.  Since  the  outbreak  of  the  war,  with 
the  food  restrictions  which  have  accompanied  it,  Rubner  has 
become  convinced  that  a  restricted  protein  dietary  is  without 
harmful  influence.  This  information  has  been  given  the 
author  through  a  reliable  source.  For  Rubner's  ideas  of 
practical  food  reform  see  p.  570. 

Hirschfeld3  finds  that  the  actual  ration  of  a  German  soldier 

1  Albertoni  and  Rossi:  "Archiv  fur  experimentelle  Pathologie  und  Pharma- 
kologie,"  1908,  Supplement,  p.  29. 

2  Rubner:    "Ueber  moderne  Ernahrungsreformen,"  Berlin,  1914. 

3  Hirschfeld:   "Archiv  fur  Physiologie,"  1903,  p.  380. 


A    NORMAL   DIET  343 

contains  98  grams  of  protein,  with  no  untoward  results.  He 
states  that  writers  on  economics,  who  believe  the  German 
populace  underfed  because  they  do  not  have  118  grams  of 
protein  daily,  are  unduly  pessimistic. 

Although,  as  has  been  stated,  the  battleground  has  been 
over  the  allowance  of  118  grams  in  Voit's  dietary,  it  will  be  sur- 
prising to  many  to  learn  that  Voit  himself  said  little  on  the 
subject.  He1  showed  that  a  vegetarian  can  live  in  nitrogenous 
equilibrium  on  a  diet  containing  48.5  grams  of  protein  and 
that  an  active  working  man  weighing  74  kilos  may  get  along 
on  less  than  118  grams.  He  discouraged  the  tendency  to  eat 
meat  in  excess.  He  also  discouraged  the  practice  of  vege- 
tarians who  overload  the  digestive  tract  with  the  coarser  kinds 
of  vegetable  foods  which  leave  large  indigestible  residues. 

It  is  not  to  be  denied  that  50  grams  of  protein  (containing 
8  grams  of  nitrogen)  are  apparently  able  to  maintain  the  adult 
body  machine  in  perfect  repair.  Vegetarians,  fruitarians2 
(who  live  on  fruit  and  nuts),  and  vigorous  adults,  who  largely 
exclude  protein  from  the  diet,  are  evidently  able  to  live  in 
health  and  strength  upon  this  quantity.  It  must  be,  however, 
that  more  than  this  amount  is  advisable  during  growth  or 
convalescence  from  wasting  disease,  or  during  the  muscular 
hypertrophy  which  accompanies  preliminary  training  for 
athletic  effort. 

Abderhalden3  mentions  the  fact  that  since  various  body 
tissues  are  constructed  of  different  proteins,  therefore  a  large 
variety  of  amino-acids  in  sufficient  quantity  must  be  available 
for  their  proper  replenishment.  Hence,  it  is  reasonable  to  as- 
sume that  an  excess  of  food  protein  is  essential  to  supply  the 
special  amino-products  for  the  synthesis  of  the  characteristic 
proteins  of  the  blood-serum  and  those  of  the  different  organs. 

It  is  certain  that  large  ingestion  of  protein  in  hot  weather 
increases  the  heat  production  with  accompanying  increase  in 

1  Voit:    "Zeitschrift  fur  Biologie,"  i88g,  xxv,  278. 

2  Jaffa:    U.  S.  Department  of  Agriculture,  1903,  Bulletin  No.  132. 

3  Abderhalden:  "Zentralblatt  fur  d.  ges.  Physiol,  und  Path.  d.  Stoffwerh- 
sels,"  1906,  i,  225. 


344  SCIENCE   OF   NUTRITION 

perspiration  (p.  235).  Meat  should  therefore  be  avoided  in 
hot  weather.  In  cold  weather  such  an  extra  heat  production 
may  produce  a  pleasurable  sensation  of  warmth.  Dr.  Folin,  in 
personal  conversation  with  the  writer,  said  that  a  dietary  of 
carbohydrates,  fat,  and  low  protein  was  easily  borne  by  an 
individual  during  the  summer,  but  during  the  winter  the  man 
complained  of  his  sensitiveness  to  cold  when  taking  the  same 
diet. 

Ranke1  describes  experiments  on  himself  (weight  =  73 
kilograms)  during  the  hottest  months  of  summer  weather  in 
Munich,  at  which  time  he  partook  of  an  ample  diet,  rich  in 
protein  (135  grams),  containing  3300  calories — a  diet  which  he 
had  enjoyed  during  the  preceding  winter.  He  had  to  force 
himself  to  eat.  He  was  first  attacked  by  catarrh  of  the  stom- 
ach, from  which  he  recovered  by  dieting,  and  subsequently 
became  infected  by  diphtheria.  He  had  formerly  suffered 
from  catarrh  of  the  stomach  while  residing  in  the  tropics. 
The  excess  of  food,  and  especially  of  protein,  threw  an  un- 
necessary burden  upon  the  heat-regulating  apparatus  which 
would  not  have  taken  place  had  the  dictates  of  the  appetite 
been  allowed  full  sway  and  had  the  ration  voluntarily  been 
reduced. 

From  the  knowledge  at  hand  there  appears  to  be  no  strongly 
substantiated  argument  why  that  portion  of  mankind  living  in 
a  cool  climate  should  not  follow  the  general  custom  of  taking 
100  grams  of  protein,  more  or  less,  in  moderate  accordance  with 
the  dictates  of  their  appetites.  Everyone  knows  that  excessive 
ingestion  of  highly  flavored  meats  results  in  jaded  appetite,  an 
automatic  signal  of  excess. 

A  similar  excess  of  food  when  given  to  dogs  results  in  vomit- 
ing. Rubner2  says  that  many  years  of  experience  with  dogs 
leads  him  to  believe  that  appetite  and  capacity  for  digestion 
and  absorption  depend  on  the  dog's  requirement  for  energy  in 
his  given  state  of  nutrition.     A  diet  which  a  dog  will  greedily 

1  Ranke:   "Zeitschrift  fur  Biologie,"  1900,  xl,  299. 

2  Rubner:    "Energiegesetze,"  1902,  p.  83. 


A   NORMAL  DIET  345 

devour  when  in  a  room  at  a  temperature  of  o°  he  will  in  part 
refuse  when  at  a  temperature  of  330. 

Eward1  writes:  "When  the  appetite  is  given  full  control 
of  what  shall  be  eaten  it  is  surprising  to  note  how  pigs  naturally 
select  the  specific  feeds  which  swine  herdsmen  have  long  since 
approved  of  as  the  best,  and,  what  is  equally  surprising,  the 
pigs  show  a  marked  avoidance  of  those  feeds  usually  considered 
as  ill  adapted  to  swine." 

While  the  protein  quantity  in  the  diet  may  vary  within 
wide  limits  with  the  taste,  the  purse,  or  the  fad  of  the  indi- 
vidual, the  quantity  of  energy  required  by  the  organism  is  a  re- 
markably constant  factor,  being  3  5  calories  per  kilogram  of  body 
weight  in  the  average  man  doing  light  work  on  a  mixed  diet. 
Comparatively  little  of  this  energy  is  furnished  by  protein. 

In  a  fasting  individual  protein  furnishes  13  and  fat  87  per 
cent,  of  the  total  heat  given  off  from  the  body. 

In  Voit's  medium  mixed  diet,  designed  for  a  laboring  man, 
the  118  grams  of  protein  furnish  about  15  per  cent,  of  the  total 
of  3055  calories. 

In  such  an  experiment  as  Siven's,  mentioned  on  page 
336,  which  represents  a  very  low  level  of  nitrogen  equilib- 
rium, the  25  grams  of  protein  ingested  furnished  100  calories 
out  of  2717  ingested  in  the  food,  or  3.6  per  cent.  However, 
since  the  total  metabolism  was  measured  as  2082  calories,  the 
protein  furnished  approximately  5  per  cent,  of  this  energy. 

Chittenden2  gives  a  dietary  containing  50  grams  of  protein 
and  2500  calories  as  sufficient  for  a  soldier  at  work.  This 
allows  8  per  cent,  of  the  total  energy  in  protein.  These  data 
may  be  thus  summarized : 

Calories  from  Calories  from  Fat 

Grams  of  Protein  Metabo-  and  Carbohydrate 

Protein  lism  in  Metabolism  in 

in  Diet.  Per  Cent.  Per  Cent. 

Starvation o  13  87 

Voit's  standard  (liberal  protein)  118  16  84 
Chittenden's   standard    (reduced 

protein) 50  8  92 

SiveVs  minimum 25  5  95 

1  Evyard:   "Proceedings  of  the  Iowa  Academy  of  Science,"  1915,  xxii,  400. 

2  Chittenden:   Loc.  oil.,  p.  254. 


346  SCIENCE   OF   NUTRITION 

The  energy  other  than  that  contained  in  protein  may  be 
given  as  carbohydrates  or  as  fat.  Voit  allows  a  laborer  500 
grams  of  starch  (2050  calories,  or  67  per  cent,  of  the  total)  as 
the  quantity  which  the  intestinal  canal  may  readily  digest, 
and  adds  56  grams  of  fat  (521  calories,  or  17  per  cent,  of  the 
total)  to  the  diet. 

It  has  already  been  observed  that  half  the  energy  may  be 
given  in  fat  and  half  in  carbohydrates  without  affecting  the 
carbohydrate  power  of  economy  over  the  protein  metabolism 
(see  p.  270). 

This  part  of  the  subject  really  becomes  a  mere  matter  of 
calculation  of  the  requirement  of  the  resting  organism,  and  the 
addition  thereto  of  sufficient  energy  to  accomplish  the  mechan- 
ical work. 

How  this  is  done  has  already  been  set  forth  in  another 
chapter.  A  bicyclist  riding  for  sixteen  hours  may  have  a 
metabolism  amounting  to  9000  calories  daily,  and  the  average 
ration  of  a  Maine  lumberman  may  rise  to  a  value  of  8000 
calories.  Champion  wrestlers  in  a  world's  contest1  may  ingest 
daily  during  their  periods  of  effort  diets  containing  protein 
217.9  grams  (35,1  grams  of  N) ;  fat,  259.5  grams;  carbohydrates, 
431  grams;  together,  5070  calories;  or  protein,  182.2  grams 
(29.2  grams  N);  fat,  204.6  grams;  carbohydrates,  392.3  grams; 
together,  4254  calories.  Much  cream  was  taken  by  these 
last-named  individuals. 

Chittenden2  has  fallen  into  error  in  the  commendation  of 
2500  to  2600  calories  as  an  ample  diet  for  a  soldier  at  drill. 
For  himself,  pursuing  a  sedentary  life,  Chittenden  prescribes 
2000  calories,  or  35  per  kilogram,  while  Mendel  requires  2448 
calories,  or  35.3  calories  per  kilogram.  These  are  entirely 
normal  values  for  people  at  light  work.  In  the  earliest  calcula- 
tions of  Voit,  in  1866,  it  was  shown  that  a  man  of  70  kilograms 
on  a  medium  mixed  diet  produced  2400  calories,  or  34.3 
calories  per  kilogram ;  and  Rubner  allows  2445  calories  to  men 

1Lavonius:    "Skan.  Archiv  fiir  Physiologie,"  1905,  xvii,  196. 
2  Chittenden:   hoc.  cit.,  p.  254. 


A  NORMAL  DIET  347 

of  70  kilograms  weight  engaged  in  occupations  involving  light 
muscular  work — such  men  as  writers,  draughtsmen,  tailors, 
physicians,  etc.  But  the  soldiers  under  Chittenden  were  put 
for  two  hours  in  the  gymnasium,  then  apparently  drilled  for 
one  hour,  and  walked  another  hour.  This  physical  work 
requires  increased  energy  from  metabolism.  It  has  been 
shown  that  to  walk  2.7  miles  in  an  hour  on  a  level  road  re- 
quires an  increased  metabolism  of  159.2  calories  in  a  man 
weighing  70  kilograms.  If  a  soldier  during  four  hours  actually 
expended  this  equivalent  mechanical  energy  in  excess  of  the 
amount  of  Professor  Mendel  in  his  laboratory,  then  his  metab- 
olism would  be  larger  than  Professor  Mendel's  by  637  calories, 
or  he  would  have  a  total  metabolism  of  3085. 

In  Chittenden's  experiments  there  was  no  analysis  of  the 
expired  air,  and  conclusions  are  drawn  from  the  maintenance 
of  body  weight. 

Several  of  the  larger-sized  soldiers  (those  who  weighed  70 
kilograms)  lost  between  3.5  and  8.5  kilograms  of  body  weight 
during  the  experiments.  Fritz,  weighing  76.0  kilograms,  lost 
3.6  kilograms  in  five  months.  Had  this  all  been  fat,  one  can 
estimate  that  its  heat  value  would  have  been  33480  calories, 
or  an  available  daily  combustion  of  body  substance  equal  to 
223  calories.  Conclusions  drawn  from  weight  alone  can  be  of 
only  the  roughest  character  (see  p.  273). 

For  ordinary  laborers,  working  eight  to  ten  hours  a  day, 
such  as  mechanics,  porters,  joiners,  soldiers  in  garrison,  and 
fanners,  3000  calories  does  not  seem  an  excessive  quantity. 

Rubner's  diet  calls  for  2868  calories.  Chittenden's  allow- 
ance (2500-2600)  is  too  low,  while  Atwater's  (3400)  ap- 
proximates that  required  by  a  farmer. 

A  third  class  are  men  at  hard  labor,  such  as  soldiers  in  the 
field,  shoemakers,  blacksmiths,  etc.  For  these  Voit  allows  a 
dietary  containing  3574  calories;  Rubner,  3362  calories;  and 
Atwater,  4150  calories.  The  differences  in  these  figures  are 
merely  differences  in  the  quantity  of  work  alone. 


348  SCIENCE   OF   NUTRITION 

In  almost  all  the  rations  given  carbohydrates  do  not  exceed 
500  grams.     The  remainder  is  made  up  of  fat. 

Atwater1  reports  the  following  dietaries  for  farmers: 

Calories. 

Farmers  in  Connecticut 3410 

"  Vermont 3635 

New  York 3785 

"  Mexico 3435 

Italy 3505 

To  this  list  may  be  added  for  farmers  in  Finland  3474 
calories,  as  found  in  the  exhaustive  studies  of  Sundstrom.2 
He  states  that  the  diet  of  the  average  Finnish  peasant  con- 
tains 136  grams  of  protein,  83  grams  of  fat,  and  580  grams 
of  carbohydrates,  which  corresponds  to  a  division  of  calories 
so  that  protein  furnishes  15  per  cent.,  fat  21  per  cent.,  and 
carbohydrates  64  per  cent,  of  the  total.  He  notes  that  if  the 
peasant's  requirement  of  energy  were  taken  in  rye  bread  alone 
124  grams  of  protein  would  be  ingested  with  it,  whereas  if  a 
milk  diet  covered  the  requirement  195  grams  of  protein  would 
be  taken.  He,  therefore,  sees  no  outlook  for  a  low  protein 
dietary  among  the  poorer  classes,  that  have  hard  work  to  do 
and  must  ingest  large  quantities  of  food  fuel. 

Woods  and  Mansfield3  report  a  dietary  study  of  a  camp  of 
fifty  Maine  lumbermen  actively  engaged  in  chopping  and  yard- 
ing logs.  The  investigation  continued  for  six  days.  The 
daily  average  ration  per  man  was  as  follows:  Protein,  164. 1 
grams;  fat,  387.8  grams;  carbohydrates,  982.0  grams;  calor- 
ies, 8083  This  dietary  would  appear  almost  fabulous  were 
it  not  for  the  fact  that  Atwater  has  actually  shown  that 
a  metabolism  equivalent  to  9300  calories  a  day  may  be  pro- 
duced by  a  man  riding  a  stationary  bicycle  for  sixteen  hours. 

Becker  and  Hamalainen4  in  Finland  have  shown  how  much 
energy  is  needed  by  people  in  various  occupations.  The  women 
may  be  first  considered.     The  work  day  was  of  eight  hours: 

1  Atwater:   Report  of  Storr's  Agricultural  Station,  1902-03,  p.  135. 

2  Sundstrom:  "Untersuchungen  iiber  die  Ernahrung  der  Landbevolkerung 
in  Finland,"  1908.  *  Woods  and  Mansfield,   Loc.  cit. 

4  Becker  and  Hamalainen:  "Skan.  Archiv  fur  Physiologie,"  1914,  xxxi,  198. 


A   NORMAL   DIET  349 

A  seamstress  sewing  with  a  needle  required  1800  calories. 

Two  seamstresses,  using  a  sewing  machine,  required  1900 
and  2100  calories,  respectively.  . 

Two  bookbinders  required  1900  and  2100  calories. 

Two  household  servants,  employed  in  such  occupations  as 
cleaning  windows  and  floors,  scouring  knives,  forks,  and 
spoons,  scouring  copper  and  iron  pots,  required  2300  to  2900 
calories. 

Two  washerwomen,  the  same  servants  as  the  last  named, 
required  2600  and  3400  calories  in  the  fulfilment  of  their 
daily  work. 

Concerning  the  fuel  requirement  for  the  occupations  of  men: 

Two  tailors  required  2400  to  2500  calories. 

A  bookbinder  required  2700  and  a  shoemaker  2800. 

Two  metal  workers,  filing  and  hammering  metals,  required 
3100  and  3200  calories. 

Two  painters,  occupied  in  painting  furniture,  required 
3200  and  3300  calories,  and  two  carpenters  engaged  in  making 
tables  required  the  same  amount  of  energy. 

Two  stonemasons  chiseling  a  tombstone  needed  4,300  and 
4700  calories. 

Two  men  sawing  wood  required  5000  and  5400  calories. 

The  proverbial  reputation  of  sawing  wood  as  a  strenuous 
occupation  has  here  its  scientific  verification  and  explains  the 
disinclination  of  the  hungry  to  engage  in  this  useful  occupation, 
as  well  as  the  unpopularity  of  charitable  wood  yards. 

Carpenter1  has  investigated  the  energy  required  for 
typewriting.  He  finds  that  the  increase  in  oxygen  absorption, 
above  the  amount  when  the  typist  is  sitting  and  reading, 
amounts  to  about  2.47  grams,  or  the  equivalent  of  8  calories 
per  thousand  words  when  the  speed  is  fifty  words  per  minute. 
This  would  aggregate  24  calories  per  hour  or  192  calories  for 
eight  hours.  This  quantity  of  energy  is  about  the  equivalent 
of  that  necessary  for  the  forward  progression  of  an  average 
man  walking  horizontally  for  one  hour  and  ten  minutes  at 

1  Carpenter:   "Journal  of  Biological  Chemistry,"  ion,  ix,  231. 


35° 


SCIENCE   OF   NUTRITION 


a  speed  of  2.7  miles  an  hour;  the  expenditure  of  energy  in 
typing  is  therefore  slight. 

A  lower  ration  than  the  lowest  here  mentioned  may  be 
allowed  to  one  who  is  confined  to  his  bed  (p.  no).  In  many 
hospitals,  however,  it  has  been  found  that  liberal  feeding  of 
the  very  poor  is  often  better  than  medicine. 

The  "standard"  dietaries  are  given  below,  not  because  they 
are  inflexible  requirements  in  any  sense  of  the  word,  but 
merely  for  the  convenience  of  the  reader.  The  individual 
standard  will  ever  be  controlled  by  climate,  the  amount  and 
kind  of  mechanical  effort;  by  appetite,  purse  and  dietetic 
prejudice. 

STANDARD  DIETARIES  FOR  A  MAN  OF  70  KILOGRAMS 

(Weights  in  Grams) 

VOIT.  RUBNER.  ATWATER. 

Light  work: 

Protein 123  100 

Fat 46  * 

Carbohydrates 377  * 

Calories 2445  2700 

Medium  work: 

Protein 118  127  125 

Fat 56  52  * 

Carbohydrates 500  509  * 

Calories.  .  .  , 3°55  2868  3400 

Hard  work: 

Protein 145  165  150 

Fat 100  70  * 

Carbohydrates 500  565  * 

Calories 3574  3362  4150 

*Carbohydrates  and  fats  to  make  up  the  fuel  value. 

Rubner1  cites  the  following  food  values  consumed  daily  per 
inhabitant  of  different  cities,  based  upon  municipal  statistics  of 
gross  consumption: 

MUNICIPAL  FOOD   STATISTICS 


• 
Protein. 

Fat. 

Carbohy- 
drates. 

Calories. 

Konigsberg 

Munich 

Paris 

London 

Grams. 
84 
96 
98 
98 

Grams. 

31 
65 
64 
60 

Grams. 
414 
492 

46S 
416 

2394 
30I4 
2903 
2665 

1  Rubner:   von  Leyden's  "Handbuch  der  Ernahrung,"  1903,  i,  160. 


A    NORMAL   DIET 


351 


In  contrast  to  this,  comparative  uniformity  hospital  dieta- 
ries, as  regulated  by  the  management  of  such  institutions, 
vary  greatly. 

Rubner1  cites  the  following  hospital  dietaries: 

HOSPITAL  DIETARIES 


Protein. 

Fat. 

Carbohy- 
drates. 

Calories. 

Munich 

Augsburg 

Halle 

Grams. 
92 

94 

92 

107 

Grams. 

54 
57 
3° 
69 

Grams. 

157 

393 
533 

1381 
1823 
2267 

England 

3266 

An  interesting  study  of  the  dietary  of  a  poorhouse  in 
Helsingfors,  Finland,  was  made  by  Elizabeth  Koch.2  A  total 
of  3355  calories  was  offered  to  each  of  five  old  men  daily  and 
2430  were  taken  per  person.  Of  the  food  offered,  1500  calories 
were  contained  in  bread.     The  dietary  was  thus  arranged: 

Breakfast.    Daily:  200  gm.  potatoes;  I  liter  skimmed  milk;  40  gm.  butter. 

Four  times  a  week,  50  gm.  salt  fish  (Stromling);  bread,  200  gm. 
Dinner.        Daily:    200  gm.  bread. 

Four  times  weekly,  100  gm.  meat;  200  gm.  potatoes. 

Twice  a  week  bean  soup.     Beets  and  barley  also  furnished. 
Supper.        Mostly  bread,  skimmed  milk,  and  wheaten  grits. 

When  taking  this  diet  the  inmates  of  the  institution  con- 
sumed an  average  of  106  grams  of  protein,  55  grams  of  fat,  361 
grams  of  carbohydrates,  and  34  grams  of  salts.  The  total 
quantity  of  milk  offered,  amounting  to  between  667  and  1000 
c.c.  daily  per  person,  was  in  each  case  completely  taken. 
Old  men  of  seventy-five  years  took  a  fair  quantity  of  food, 
as  appears  from  the  following  analysis : 


Age. 

Weight. 

Height. 

Calories  in 
Food. 

Calories  per 
Kg. 

Years. 

Kg. 

M. 

M . . . . 

54 

62.5 

1.64 

2307 

36.9 

I.. 

60 

72.5 

1.76 

2790 

38.5 

Mu.  .  . 

70 

70.5 

I.65 

2565 

30-4 

A 

75 

65.0 

1.64 

2379 

30-5 

L 

79 

60.0 

1.65 

2108 

35-i 

1  Rubner:   Loc.  cit.,  p.  157. 

2  Koch,  E.:   "Skan.  Archiv  fur  Physiologie,"  1911,  xxv,  315. 


352  SCIENCE   OF   NUTRITION 

The  author  concludes  that  the  quantity  of  food  needed  by 
old  men  is  slightly  below  the  normal  (see  p.  129). 

The  population  of  a  city  will  ordinarily  sustain  itself  in 
accordance  with  its  needs.  In  public  institutions,  however, 
such  as  poorhouses,  prisons,  asylums,  hospitals,  and  in  military 
and  naval  establishments,  scientific  knowledge  of  the  needs  of 
the  individual  becomes  a  very  important  consideration.  The 
prolonged  endurance  of  an  army  of  soldiers  is  just  as  dependent 
on  an  ample  army  ration  as  is  the  battleship  dependent  on  its 
supply  of  fuel.  Not  only  the  quantity  of  the  food  makes  for 
the  well-being,  but  it  must  taste  well.  No  amount  of  actual 
fuel  value  could  compel  the  American  soldiers  of  the  Spanish- 
American  war  to  eat  the  "embalmed  beef"  furnished  by  the 
Government.  The  flavor  is  to  the  man  what  oil  is  to  the  ma- 
chinery of  the  battleship.  Without  flavor  in  the  food  the 
digestive  apparatus  does  not  run  smoothly.  In  ordinary 
civilized  life  even  psychical  influences  act.  The  cloth  on  the 
table  must  be  spotless,  and  the  environment  inviting. 

In  the  process  of  manufacture  of  Liebig's  extract  of  beef 
muscle  creatin  is  largely  converted  into  creatinin.  Such  an 
extract,  which  contains  also  xanthin,  is  not  strictly  a  food, 
since  its  constituents  are  largely  ready  for  elimination  in  the 
urine.1  Biirgi2  shows  that  if  meat  extract  be  administered  it 
is  excreted  in  the  urine,  excepting  4.57  per  cent,  of  its  nitrogen, 
14.85  per  cent,  of  its  carbon,  and  17.55  Per  cent,  of  its  energy 
content. 

Its  value  lies  in  its  flavor,  which  promotes  the  proper  flow 
of  the  digestive  juices.3 

It  may  be  incidentally  remarked  that  the  principal  value  of 
many  "patent"  foods,  "invalid"  foods,  etc.,  lies  in  their  flavor. 
If  agreeable  to  the  taste  of  the  individual  they  usually  afford  a 
harmless  indulgence.  That  beef,  milk,  cream,  butter,  and  rice 
are  quite  as  suitable  for  all  the  purposes  of  proper  living  is 
a   fact  not  sufficiently  advertised.     The   old-time  fraud  of 

1  Rubner:   "Zeitschrift  fur  Biologie,"  1883,  xix,  343. 

2  Biirgi:  "Archiv  fur  Hygiene,"  1904,  li,  1. 

3  Voit:   "Stoffwechsel,"  1881,  p.  449. 


A   NORMAL  DIET  353 

"patent"  foods  being  "brain  restorers"  is  as  foolish  a  lie  as  can 
be  written. 

One  takes  as  food  milk,  eggs,  various  meats,  such  as  beef, 
veal,  pork,  mutton,  fish;  also  cereals,  such  as  bread,  rice,  corn, 
macaroni,  beans,  and  peas.  Sometimes  alcoholic  beverages 
are  added.  The  calorific  values  may  be  calculated  by  de- 
termining the  composition  of  the  various  nutrient  materials 
by  analysis  and  by  multiplying  the  number  of  grams  of 
each  constituent  by  the  factor  which  represents  its  fuel  value 
to  the  organism  (see  p.  42). 

As  a  simple  illustration  of  this  the  following  experiment  of 
Rubner1  may  be  cited:  A  man  weighing  46  kilograms  ate  noth- 
ing but  eggs  for  two  days — 22  on  the  first  day  and  20  on  the 
second.  The  22  eggs  contained  1017.4  grams  of  material;  the 
20  eggs,  878.8  grams,  an  average  of  948.1  grams  per  day.  Since 
100  grams  of  egg  contain  14. 1  grams  of  protein  and  10.9  grams 
of  fat,  948.1  grams  would  contain  a  daily  allowance  of  133.6 
grams  of  protein  and  103  grams  of  fat.  If  Rubner's  standard 
values  for  the  energy  content  are  used,  the  result  will  be  as 
follows: 

133.6  grams  protein  X  4.1  =     547  calories. 
103.3  grams  fat  X  9.3  =     961  calories. 


Total =  1508  calories, 

or  ^$  calories  per  kilogram. 

This  dietary  of  eggs  was,  therefore,  nearly  sufficient  for  the 
fuel  requirement  of  this  undersized  individual.  Notwithstand- 
ing the  large  amount  of  protein  in  the  dietary  there  was  a  loss 
of  body  protein  equal  to  7.5  grams  per  day. 

The  results  of  an  exclusive  milk  diet  are  thus  summarized 
by  Rubner:2  Milk  (2438  grams),  containing  84  grams  of  protein 
and  two-thirds  of  the  requirement  of  energy  for  the  individual, 
produced  a  deposit  of  protein  equal  to  6.7  grams  daily  (p.  279). 
To  cover  a  requirement  of  2400  calories  daily  3410  grams  of 
milk  would  be  needed,  which  contain  140  grams  of  protein. 

1  Rubner:   "Zeitschrift  fur  Biologie,"  1879,  xv,  127. 

2  Rubner:  von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1903,  i,  132. 

23 


354  SCIENCE   OF   NUTRITION 

For  a  laboring  man  with  a  requirement  of  3080  calories, 
4380  grams  of  milk  with  180  grams  of  protein  would  be 
necessary. 

Thomas1  drank  10.7  liters  of  whole  milk  (6781  calories) 
in  one  day,  taking  it  up  to  the  limit  of  his  capacity.  Of  53.3 
grams  of  nitrogen  in  the  milk,  28.7  grams  appeared  in  the  urine 
of  the  day  and  21.1  grams  were  added  to  the  body.  Of  67.4 
grams  of  salts  contained  in  the  milk,  36.9  grams  were  present 
in  the  urine  of  the  twenty-four-hour  period  and  29.5  grams  were 
passed  in  the  feces  attributable  to  the  diet;  the  power  to 
absorb  such  a  diet  was  therefore  great.  Dried  milk  powder 
preparations  were  absorbed  with  as  great  ease  as  whole 
milk. 

It  is  evident  that  milk  with  its  high  protein  content  is  a 
food  par  excellence  for  the  growing  organism  or  for  the  invalid 
convalescing  from  wasting  disease.  It  contains  too  large  an 
amount  of  protein  for  a  normal  adult.  A  mixture  of  milk, 
toast,  and  cream  (creamed  milk-toast)  may  produce  a  modified 
milk  diet  of  proper  value  and  easy  digestibility.  An  exclusive 
milk  diet  contains  too  little  iron  for  the  needs  of  a  normal 
adult. 

Moritz2  recommends  milk  alone  in  treatment  of  obesity, 
in  quantities  varying  between  1.5  and  2.5  liters  daily.  The 
normal  weight  in  kilograms  of  the  individual  is  calculated  from 
his  height,  and  each  kilogram  of  such  weight  is  provided  with 
16  to  17  calories  in  the  diet,  an  amount  which  is  contained  in 
25  c.c.  of  milk.  Should  the  normal  weight  be  80  kilograms, 
2000  grams  of  milk  are  administered  daily  in  five  portions. 
Such  treatment  brings  about  a  considerable  loss  in  body 
weight,  and,  although  some  body  nitrogen  is  lost,  a  state  of 
weakness  does  not  ensue. 

Rubner  finds  that  1500  grams  of  good  white  bread  contain- 
ing 104.4  grams  of  protein  will  maintain  a  working  man  in 
nitrogenous  and  calorific  equilibrium. 

1  Thomas:    "Archiv  fiir  Physiologie,''  iooo,  p.  417. 

2  Moritz:    "Munchener  medizinische  Wochenschiift,''  1908,  lv,  1569. 


A   NORMAL  DIET  355 

Thomas1  took  on  three  successive  days  an  average  of 
2760  grams  of  fresh  bananas  which  were  not  completely  ripe, 
and  to  this  he  added  300  grams  of  sugar.  This  gave  a  total 
intake  of  4.32  grams  of  nitrogen  and  2741  calories  daily. 
Although  a  preliminary  diet  of  starch  and  sugar  had  reduced 
the  urinary  nitrogen  to  3  grams  at  the  beginning  of  the  experi- 
ment, nitrogen  equilibrium  could  not  be  obtained  when  the 
above  noted  amount  of  bananas  was  ingested.  The  unripened 
starch  of  the  banana  is  eliminated  in  the  feces.  Ripe  banana 
in  which  almost  all  the  starch  has  been  converted  into  glucose 
is  very  completely  digestible.  Whereas  five  parts  of  potato 
protein  may  replace  four  of  body  protein  in  establishing 
nitrogen  equilibrium,  the  protein  .of  banana  is  not  so  efficient. 
Yet  in  tropical  countries,  such  as  the  sea-coast  of  East  Africa, 
the  Congo,  and  in  the  Pacific  Islands,  during  the  six  months  of 
the  rainy  season  (in  which  the  banana  is  ripe),  it  furnishes 
almost  the  exclusive  diet  of  the  natives.  It  is  preferred  to 
potatoes  because  it  can  be  obtained  almost  without  labor. 
Banana  flour  is  also  prepared  in  these  localities  by  drying 
unripe  bananas  in  the  sun. 

If  water  be  taken  when  the  stomach  is  empty  it  quickly 
passes  through  the  pylorus  into  the  intestine.  Taken  with 
food,  however,  its  exit  from  the  stomach  is  considerably 
delayed;  the  delay  accounts  for  some  of  the  pleasure  of  after- 
noon tea  when  taken  with  toast.  Beer  remains  in  the  stom- 
ach longer  than  water,  and  this  may  be  due  to  the  extractive 
substances  or  to  a  narcotizing  effect  upon  the  musculature  of 
the  stomach.2 

Atwater  and  Benedict3  have  conclusively  shown  that 
alcohol  may  be  used  in  the  economy  in  place  of  isodynamic 
quantities  of  carbohydrates  and  fats.  The  following  table 
shows  the  average  of  experiments  on  a  resting  individual  which 
lasted  twenty-three  days: 

1  Thomas:   "Archiv  fur  Physiologie,"  1010,  Suppl.,  p.  29. 

2  Grobbels:  "Zeitschrift  fiir  physiologische  Chemie,"  1914,  lxxxix,  1. 

3  Atwater  and  Benedict:  "Memoirs  of  the  National  Academy  of  Sciences," 
Washington,  1902,  viii,  231. 


356  SCIENCE   OF   NUTRITION 

INFLUENCE   OF   ALCOHOL   ON  METABOLISM 


Dura- 
tion in 
Days. 

In  the  Food  in  Grams. 

Alco- 
hol. 

Cal. 

in 
Food. 

Cal.  of 
Metabo- 
lism. 

Protein. 

Fat. 

Car- 
bohy- 
drates. 

Protein 
Balance. 

Ordinary  diet...  . 
Alcohol-contain- 
ing diet 

*3 

10 

114 
115 

69 

47 

354 
2  73 

72.2 

2496 
2488 

2221 
2221 

—  2.0 
-3-8 

Atwater  and  Benedict  employed  diets  containing  about 
2500  calories  for  a  man  at  rest  and  3500  for  a  man  at  work. 
During  the  alcohol  days  500  of  the  calories  were  supplied  in 
72  grams  of  alcohol,  or  about  what  is  contained  in  a  bottle 
of  claret.  The  metabolism  of  the  individual  as  expressed  in 
calories  was  unchanged  by  the  addition  of  alcohol  to  the  diet. 
The  alcohol  was  given  in  six  small  doses  and  98  per  cent,  was 
burned  by  the  organism. 

On  the  ordinary  diet  33.7  grams  of  fat  were  daily  added  to 
the  body,  and  on  the  alcohol  days  34.1  grams.  These  very 
valuable  observations  make  it  evident  that  alcohol  is  not  a 
direct  cause  of  obesity.  If,  however,  a  young  man  having 
acquired  certain  dietary  habits  at  home  continues  the  same 
diet  at  college  and  begins  to  drink  "in  moderation"  besides, 
his  increasing  rotundity  as  he  returns  on  his  vacations  can  be 
readily  explained  by  the  sparing  influence  of  alcohol  upon  the 
fat  in  his  diet. 

A  liter  of  German  beer  contains  3  to  4  per  cent,  of  alcohol 
and  5  to  6  per  cent,  extractives.  It  yields  450  calories  to  the 
body,  only  half  being  derived  from  alcohol,  the  rest  from  the 
dextrin  and  protein-like  extractives.  Here  is  a  material 
whose  "fattening"  properties  may  be  very  highly  considered. 

It  is  reported  that  alcohol  is  present  in  normal  human 
blood  to  the  extent  of  3  parts  in  100,000.  When  alcohol  is 
drunk  it  passes  into  the  blood  as  such,  and  as  much  as  2  parts 
in  1000  has  been  found  in  the  blood  of  a  drunken  man  by 


A   NORMAL   DIET  357 

Schweisheimer.1  According  to  this  author,  the  intensity  of 
the  drunkenness  depends  on  the  concentration  of  alcohol  in 
the  blood.  A  maximum  concentration  is  reached  about  an 
hour  and  a  half  to  two  hours  after  drinking  and  may  remain 
high  for  five  hours.  Those  who  are  accustomed  to  alcohol 
oxidize  it  all  in  seven  and  a  half  hours,  whereas  those  who  have 
been  abstainers  require  twice  that  time. 

It  is  interesting  that  although  alcohol  ingestion  reduces 
the  respiratory  quotient  after  it  has  been  given,  it  has  never 
been  found  to  reduce  it  to  such  an  extent  as  to  indicate  that  it  is 
the  main  source  of  the  energy  supply  of  the  body. 

An  experiment  by  Durig2  showed  that  after  giving  30 
grams  of  fructose  to  a  man  every  hour  the  respiratory  quotient 
rose  to  unity;  but  if  30  c.c.  of  alcohol  were  given  about  the 
same  time  the  respiratory  quotient  was  depressed  to  about 
0.80.  Alcohol  was,  therefore,  in  large  measure  oxidized  in- 
stead of  sugar,  but  the  respiratory  quotient  did  not  approxi- 
mate 0.67,  the  quotient  for  alcohol  itself,  as  would  have  been 
the  case  if  the  source  of  energy  had  been  exclusively  alcohol 
(see  p.  298).  These  authors  find  no  summation  of  dynamic 
effect  when  alcohol  and  carbohydrate  are  oxidized  together 
(see  p.  298). 

Voltz  and  Dietrich3  have  given  dogs  2  c.c.  of  alcohol  per 
kilogram  of  body  weight.  After  ten  hours  only  73  per  cent, 
of  the  material  had  been  oxidized,  or  enough  to  provide  for 
43  per  cent,  of  the  energy  requirement  of  the  time.  About 
90  per  cent,  was  oxidized  in  fifteen  hours,  but  it  required 
about  eighteen  to  twenty  hours  for  the  dog  to  rid  himself  of 
the  material.  Alcohol,  therefore,  is  not  a  quickly  oxidizable 
substance,  but  it  remains  in  the  blood  a  long  time.  Although 
sugar  may  entirely  displace  fat  metabolism,  alcohol  can  only 
in  part  displace  carbohydrate  from  its  part  in  metabolism. 

All  alcoholic  beverages  are  taken  with  a  twofold  object: 
first,  the  desire  for  flavor,  and  second,  for  stimulation;  their 

1  Schweisheimer:  "Deutsches  Archiv  fiir  klinische  Medizin,"  1913,  cix,  271. 

2  Togel,  Brezina,  and  Durig:    "Biochemische  Zeitschrift,"  1913,  1,  298. 

3  Voltz  and  Dietrich:  Ibid.,  1914,  lxviii,  118. 


358  SCIENCE   OF   NUTRITION 

food  value,  as  above  described,  is  usually  little  considered.  In 
general,  it  may  be  said  that  alcohol  as  a  stomachic  is  valueless 
when  the  gastric  juice  is  normal,  but  is  beneficial  in  cases  of 
supersecretion,  hypochlorhydria,  and  loss  of  appetite.  Under 
these  circumstances  small  amounts  of  beverages  containing  5  to 
10  per  cent,  of  alcohol  are  sufficient  for  all  purposes.1 

In  the  light  of  the  social  evils  which  accompany  the  excess- 
ive use  of  alcohol  as  a  beverage  there  is  no  doubt  that  its  total 
prohibition — if  this  were  possible — would  make  for  the  public 
weal  and  improve  the  physical  and  moral  condition  of  man- 
kind. 

The  subject  of  alcohol  could  be  spun  out  into  a  considerable 
story,  but  for  further  details  the  reader  is  referred  to  other 
sources.2 

The  ash  constituents  of  a  dietary  are  certainly  of  impor- 
tance.3 In  fasting  there  is  a  constant  loss  of  salts  from  the 
body.  There  is  apparently  a  "wear-and-tear"  metabolism  of 
the  bones  (see  p.  99)  which  must  be  replaced  by  ingested 
salts. 

The  minimum  amount  of  calcium  needed  in  the  daily  diet 
in  order  to  establish  "calcium  equilibrium"  is  unknown. 
Benedict's  fasting  man  eliminated  0.138  gram  of  calcium  oxid 
in  the  urine  of  the  thirty-first  day  of  his  fast. 

From  the  work  of  Bertram,4  it  appears  that  a  man  can  be 
maintained  in  calcium  equilibrium  when  the  diet  contains 
0.4  gram  of  calcium  oxid.  Herxheimer5  obtained  the  same 
result  when  a  man  took  0.86  gram  of  calcium  oxid. 

German  authorities  state  that  a  man  requires  about  1.5 
grams  of  calcium  oxid  daily.     Thus  Hornemann6  places  the 

1Zitowitsch:    Abstract  in  "Biochem.  Centralblatt,"  1905,  iv,  574. 

2  "The  Use  of  Alcohol  in  Medicine":  F.  G.  Benedict,  A.  R.  Cushny,  S.  J. 
Meltzer,  Graham  Lusk,  "Boston  Medical  and  Surgical  Journal,"  io°2,  cxlvii, 
31;  "Bibliograpbie  der  gesammten  wissenschaftlichen  Literatur  liber  den  Alko- 
hol  und  den  Alkoholismus,"  1904,  by  Emil  Abderhalden. 

3  For  the  older  literature  see  Albu  and  Neuberg:  "Physiologie  und  Path- 
ologie  des  MineralstofTwechsels,"  1906. 

4  Bertram:    "Zeitschrift  fiir  Biologie,"  1878,  xiv,  354. 

6  Herxheimer:     "Berliner  klinische  Wochenschrift,"  1897,  xxxiv,  423. 
6  Hornemann:    "Zeitschrift  fiir  Hygiene,"  1913,  lxxv,  553. 


A    NORMAL   DIET 


359 


requirement  of  calcium  oxid  at  1.7  grams  and  of  iron  at  55 
milligrams,  the  sodium  chlorid  balance  being  maintained 
with  5  grams  of  that  salt  daily,  or  half  to  one-quarter  the 
amount  usually  taken. 

Tigerstedt1  reports  that  the  diet  ot  the  Finns  contains 
between  2  and  6  grams  of  calcium  oxid  daily,  and  this  on 
account  of  the  large  intake  of  milk  (see  p.  348),  which  aver- 
ages 1570  c.c.  for  men  and  913  c.c.  for  women. 

In  contrast  with  this,  the  ordinary  American  diet  of  the 
average  inhabitant  of  the  Eastern  States,  as  studied  by  Sher- 
man, Mettler,  and  Sinclair2  presents  a  sorry  spectacle. 

The  salt  content  of  the  dietaries  taken  by  the  people  of 
the  two  nations  may  be  thus  contrasted : 

ASH  CONTENT  OF  ORDINARY  DIETARIES,  WEIGHTS  IN  GRAMS 


Calories 

Finnish. 

American. 

in  Diet. 

P20i. 

Ca.O. 

6.IO 

3-79 
4.02- 

3-5i 
2.96 
2.85 

Mg.O. 

PiOi. 

Ca.O. 

Mg.O. 

Over  4000.  .  . 
4000-3500. 
3500-3000. 
3000-2500. . . 
2500-2000   . . 
2000-1500. . . 

10.S6 
9.46 
8.18 
6-93 
5-64 

5-12 

2.02 
1.85 

i-53 
1.23 
1.03 
0.78 

4.24 
3.22 

3-29 
3.20 
2.06 
1.84 

0.79 
O.04 
0.99 
0.92 
0.36 
0.68 

0.89 
0.51 
0.50 
0.46 
0.32 
0.23 

Tigerstedt  points  out  that  this  difference  in  the  salt  in- 
take of  the  different  peoples  is  due  to  the  fact  that  the  Ameri- 
can subjects  took  an  average  of  only  250  c.c.  of  milk  in  their 
diets  daily.  As  pointed  out  by  Sherman,  the  American 
family  has  only  to  drink  more  milk  or  eat  more  cheese  in  order 
to  raise  the  ash  content  of  the  dietary.  Those  in  charge  of 
the  food  supply  of  institutions  should  not  forget  the  impor- 
tance of  milk,  and  every  care  should  be  exercised  to  prevent 
the  cost  of  good  milk  from  becoming  prohibitive. 

1  Tigerstedt,  R.:    "Skan.  Archiv  ftir  Physiologie,"  1911,  xxiv,  97. 

2  Sherman,  Mettler,  and  Sinclair:  U.  S.  Dept.  of  Agriculture,  Office  of 
Experiment  Stations,  19 10,  Bulletin  No.  227  A.  Table  giving  the  ash  constit- 
uents of  the  edible  portions  of  various  food  materials  is  given  in  this  bulletin 
on  p.  41. 


36° 


SCIENCE   OF  NUTRITION 


The  American  families  were  reported  to  consume  between 
35  and  7  milligrams  of  iron  daily,  the  amount  ingested  running 
almost  parallel  with  the  intake  of  protein  in  the  food.  This  is 
much  less  than  the  minimum  called  for  by  Horneman. 

The  question  of  the  minimal  quantity  of  ash  intake  for 
human  beings  is  far  from  settled. 

The  following  table,  compiled  from  part  of  the  data  pre- 
sented by  Sherman1  and  by  Sherman  and  Gettler,2  gives  the 
ash  content  of  various  edible  foods: 


ASH  CONTENT  OF  THE  EDIBLE  PORTION  OF  SOME  COMMON 

FOODS 


Beefsteak,  lean. .  .  . 

Eggs 

Milk,  whole 

Cornmeal 

Oatmeal 

Rice,  polished 

Wheat  flour 

Wheat,  entire  grain 
Beans,  lima,  dried.. 
Beans,  string,  fresh. 

Cabbage 

Corn,  sweet 

Peas,  dried 

Potatoes 

Spinach 

Turnips 

Apples 

Raisins 


In  100  Grams  Fresh  Substance. 


Iron. 


Mg. 

3-8 
3-° 
0.2 
1.1 

3-7 
0.7 

i-5 

5-2 

7.2 
1.6 

O.Q 

o.S 
5-6 
1.2 
3-8 
0.6 

0.3 
3-6 


Cal- 
cium. 


Mg. 

8 

67 


93 

8 
26 
44 
7i 

49 

100 

11 

64 
10 

57 


Magne- 
sium. 


Mg. 

24 

9 


27 

30 
170 
1S7 

14 

145 

169 
8 
9 


Sodium 


Mg. 
67 
15 
51 

81 
21 

69 
106 

245 


118 
19 

59 

15 

141 


Potas- 
sium. 


Mg. 

35 

14 

142 

380 

68 

146 

5i5 

1743 

243 

880 
440 

332 
125 
830 


Phos- 
phorus. 


Mg. 
22 
16 

94 

380 

89 

86 

469 

336 

27 

397 
61 

5i 

13 

126 


Chlorin. 


Mg. 

5° 
100 
120 

35 
50 
76 
88 

25 

13 

40 
3° 

40 

4 
70 


Meat,  eggs,  oatmeal,  unmilled  wheat,  and  green  vege- 
tables contain  much  iron.  Milk,  polished  rice,  and  white 
flour  contain  little  iron.  Milk,  oatmeal,  and  dried  beans 
furnish  large  amounts  of  calcium. 

Not  only  is  the  quantity  of  the  ash  constituents  of  signif- 

1  Sherman:   "The  Chemistry  of  Food  and  Nutrition,"  New  York,  191 1. 

2  Sherman  and  Gettler:  "Journal  of  Biological  Chemistry,"  1911-12,  xi, 
323- 


A  NORMAL  DIET  36 1 

icance,  but  Sherman  and  Gettler1  have  shown  the  importance 
of  the  acid  or  base-forming  potency  of  the  ash  of  different 
foods.  Thus,  a  dietary  which  contained  3000  calories,  300 
calories  being  in  potato,  was  given  to  a  man,  and  then  the 
potato  was  replaced  by  rice  containing  300  calories.  The 
result  of  the  change  was  an  increase  of  50  per  cent,  in  the 
titratible  acidity  of  the  urine  and  an  increase  in  the  amount 
of  ammonia  excreted. 

Blatherwick2  has  continued  investigations  along  these 
lines,  which  show  that  foods  which  have  a  preponderance  of 
base-forming  elements  lead  to  the  formation  of  a  urine  less 
acid  than  the  normal.  Such  foods  are  potatoes,  oranges, 
raisins,  apples,  and  bananas,  and  these  are  very  efficient  in 
reducing  the  acid  output.  Tomatoes  are  less  valuable  in  this 
respect.  Rice  and  whole  wheat  bread  increase  urinary 
acidity.  Plums,  prunes,  and  cranberries,  through  their  con- 
tent of  benzoic  acid,  increase  the  urinary  acidity.  Blather- 
wick notes  that  the  hydrogen  ion  concentration  of  thirty 
urines  obtained  from  vegetarians  was  —6.64,  in  contrast  with 
a  value  of  —5.98  reported  by  Henderson  and  Palmer  for  the 
urines  of  persons  living  on  a  mixed  diet,  and  he  emphasizes 
the  close  relationship  between  the  hydrogen  ion  concentration 
of  the  urine  and  its  solvent  power  over  uric  acid.  These 
findings  are,  therefore,  in  accord  with  those  of  Hindhede  (p. 
34 1 )  and  should  establish  the  potato  upon  a  high  plane  of 
dietary  dignity. 

To  arrange  a  proper  dietary  for  a  given  individual  or 
group  of  individuals  the  very  complete  and  valuable  tables  of 
Atwater  will  be  found  most  practical.  They  are  placed  in  an 
appendix  at  the  end  of  this  volume  for  the  benefit  of  the  stu- 
dent who  may  desire  to  apply  in  practice  his  knowledge  of  the 
general  laws  of  metabolism. 

Underfed  or  overfed  individuals  may  alike  become  objects 
of  commiseration  and  proper  subjects  for  rehabilitation. 

1  Sherman  and  Gettler:   Loc.  cit. 

2  Blatherwick :    "Archives  of  Internal  Medicine,"  1914,  xiv,  409. 


CHAPTER  XIII 

THE  NUTRITIVE  VALUE  OF  VARIOUS   MATERIALS 
USED  AS  FOODS 

In  1897  Eijkman1  published  the  observation  that  the 
disease  beriberi  was  due  to  a  one-sided  diet  of  polished  rice, 
and  that  if  rice  were  not  milled,  but  eaten  with  its  peri- 
carp, beriberi  did  not  ensue.  Eijkman2  also  made  the  very 
valuable  discovery  that  pigeons,  when  fed  with  polished  rice, 
developed  a  polyneuritis  analogous  to  that  found  in  human 
beriberi,  and  that  the  addition  of  rice  bran  (rice  polishings) 
to  the  diet  prevented  this  condition.3 

About  this  same  time  Rohmann4  found  that  if,  instead 
of  natural  foods,  purified  materials,  such  as  casein,  egg- 
albumin,  vitellin,  potato  starch,  wheat  starch,  and  oleomar- 
garin,  together  with  the  proper  salts,  were  mixed  and  given 
to  mice,  their  offspring  were  difficult  to  rear  with  this  food 
and  that  no  living  young  could  be  obtained  from  them.5 
These  experiments  appeared  difficult  of  interpretation. 

In  reality,  the  work  of  Eijkman  and  of  Rohmann  was 
the  beginning  of  a  scientific  knowledge  of  the  so-called 
"deficiency  diseases."  It  now  appears  that  a  proper  diet  for 
growth  or  maintenance  must  contain  not  only  protein,  fat, 
carbohydrate,  and  salts,  but  also  some  substances  existing  in 
natural  foods,  in  very  minute  quantities,  which  are  absolutely 
essential  to  the  harmonious  fulfilment  of  the  life  processes. 
It  should  be  added  that  Rohmann  denies  the  necessity  of 
these  accessory  substances. 

1  Eijkman:    "Virchow's  Archiv,"  1897,  cxlix,  187. 

2  Eijkman:   Ibid.,  1897,  cxlviii,  523. 

3  For  useful  reference  consult  Vedder,  E.  B.:  "Beriberi,"  New  York,  1913. 

4  Rohmann:   "Klinische  therapeutische  Wochenschrift,"  1902,  No.  40. 

6  Consult  Osborne  and  Mendel:  Carnegie  Institution,  Publication  156, 
191 1 ;  Rohmann:  "Ueber  kiinstliche  Ernahrung  und  Vitamine,"  Berlin,  1916. 

362 


NUTRITIVE   VALUE   OF   MATERIALS   USED   AS   FOODS       363 

Another  pioneer  in  this  field  was  Gowland  Hopkins,1 
who  wrote  in  1906,  "No  animal  can  live  on  a  mixture  of 
pure  protein,  fat,  and  carbohydrate,  and  even  when  the 
necessary  inorganic  material  is  carefully  supplied  the  animal 
still  cannot  flourish.  The  animal  is  adjusted  to  live  either 
on  plant  tissues  or  the  tissues  of  other  animals,  and  these 
contain  countless  substances  other  than  proteins,  carbo- 
hydrates, and  fats.  ...  In  diseases  such  as  rickets  and, 
particularly,  in  scurvy  we  have  had  for  long  years  knowledge 
of  a  dietetic  factor;  but  though  we  know  how  to  benefit 
these  conditions  empirically,  the  scale  errors  in  the  diet  are 
to  this  day  quite  obscure.  .  .  .  Scurvy  and  rickets  are  con- 
ditions so  severe  that  they  force  themselves  on  our  atten- 
tion; but  many  other  nutritive  errors  affect  the  health  of 
individuals  to  a  degree  most  important  to  themselves,  and 
some  of  them  depend  upon  unsuspected  dietetic  factors." 

The  study  of  the  "accessory  factors"  of  diet,  a  term  used 
by  Hopkins,  has  been  in  the  hands  and  heads  of  some  of  the% 
ablest  physiologic  chemists  during  the  past  ten  years,  and  it 
is  extremely  difficult,  perhaps  impossible,  to  write  of  the 
subject  and  do  even-handed  justice  toward  the  various  con- 
tributors in  the  field.  Hofmeister  defines  the  unknown  but 
beneficent  factors  alluded  to  here  as  "accessory  food-stuffs," 
and  Funk  has  called  them  "vitamins."2  Objection  is  made 
to  the  term  "accessory"  on  the  ground  that  it  implies  some- 
thing non-essential,  and  to  the  term  "vitamin"  on  the  ground 
that  there  is  no  evidence  that  the  substance  or  substances 
in  question  are  amins,  nor  that  they  are  more  valuable  to 
life  than  other  substances — epinephrin,  for  example.  In 
acknowledgment  of  this  insufficiency  of  information,  McCol- 
lum3  suggests  the  provisional  use  of  two  terms,  the  "fat- 
soluble  A"  and  the  "water-soluble  B,"  as  representing  the 
factors  necessary  for  adequate  growth.     The  "water-soluble 

1  Hopkins,  F.  G.:   "Analyst,"  1906,  xxxi,  391. 

2  Funk:  "Ergebnisse  der  Physiologie,"  1913,  xiii,  126. 

3McCollum,  E.  V.:    "Journal  of  Biological  Chemistry,"  1916,  xxv,  105. 


364  SCIENCE   OF  NUTRITION 

B"  cures  beriberi  and  is  regarded  as  identical  with  Funk's 
"vitamins." 

For  the  sake  of  simplicity,  the  word  "vitamin"  may  be 
retained  provisionally  to  express  the  group  of  as  yet  uniden- 
tified substances  which  cannot  at  present  be  classified  with 
the  familiar  nutrients,  proteins,  fats,  carbohydrates,  inorganic 
salts,  and  water,  upon  which  the  harmonious  behavior  of  the 
organism  depends  and  which  are  ordinarily  ingested  in  traces 
in  the  food.  The  term  "food  hormone"  is  probably  a  more 
rational  expression  of  what  the  vitamins  signify  (see  p.  378). 

Interwoven  with  the  experimental  work  upon  the  sub- 
ject of  the  vitamins  has  been  work  upon  the  relative  value 
of  different  proteins  in  nutrition.  A  diet  may  yield  sufficient 
energy  to  maintain  the  organism  and  yet  be  a  deficient  dietary 
in  that  it  lacks  vitamins  or  contains  insufficient  salts  or  too 
little  protein  or  protein  of  low  nutritive  value. 

Stepp1  showed  that  when  mice  were  fed  with  bread  baked 
with  a  little  milk  this  formed  a  complete  diet,  but  if  this 
diet  were  first  extracted  with  alcohol  and  ether  the  animals 
all  died.  He2  further  reported  that  the  addition  of  salts  or 
fat  or  lecithin  or  cholesterol  to  the  extracted  bread  was 
without  beneficial  influence  when  it  was  given  to  mice. 
However,  the  addition  of  ether-alcohol  extracts  from  skimmed 
milk,  from  egg-yolk,  or  from  calf's  brains  to  bread  which  had 
been  extracted  furnished  a  diet  capable  of  supporting  mice. 
In  a  later  paper  Stepp3  reported  that  ether  extraction  fails  to 
remove  the  accessory  substance  necessary  to  life,  whereas 
alcohol  accomplishes  this  result;  he  therefore  concludes  that 
the  significant  substance  is  not  a  fat. 

In  191 2  Hoist  and  Frolich4  reported  that  if  guinea-pigs 
were  fed  with  a  one-sided  diet  of  white  bread,  or  with  polished 
rice  or  other  milled  grains,  they  invariably  died,  usually  in 
about  four  weeks.     They  always  showed   loose   teeth   and 

1  Stepp,  W.:   "Biochemische  Zeitschrift,"  1909,  xxii,  452. 

2  Stepp,  W.:   "Zeitschrift  fur  Biologie,"  1911-12,  lvii,  135. 

3  Stepp,  W.:   Ibid.,  1913,  lxii,  405. 

4  Hoist  and  Frolich:   "Zeitschrift  fur  Hygiene,"  191 2,  lxxii,  1. 


NUTRITIVE   VALUE    OF   MATERIALS    USED   AS   FOODS       365 

usually  hyperemic  gums.  Hemorrhages  appeared,  some- 
times in  the  skin,  but  more  usually  at  the  knee-joints  and  at 
the  cartilages  of  the  ribs,  and  there  were  microscopic  changes 
in  the  bone-marrow.  All  these  phenomena  are  in  entire  ac- 
cord with  the  manifestations  of  human  scurvy.  It  is  im- 
portant to  remember  that  it  has  never  been  demonstrated 
that  any  kind  of  unmilled  grain  will  produce  scurvy.  Mate- 
rials in  the  pericarp  are,  therefore,  essential  to  health.  As 
antidotes  to  foods  which  produce  scurvy,  fresh  vegetables, 
dried  peas,  lime-juice,  or  fermented  liquors  (wines,  beer)  are 
antiscorbutic  and  cure  human  scurvy  as  well  as  the  form 
artificially  induced  in  animals.  Drying  or  heating  some  of 
the  effective  substances  to  no0  reduces  the  antiscorbutic 
effect. 

Hess1  reports  that  in  an  asylum  where  infants  were  fed 
with  pasteurized  milk  during  a  period  of  four  months  scurvy 
developed,  accompanied  by  a  stunting  in  the  normal  growth 
of  the  infants.  This  was  at  once  corrected  by  the  adminis- 
tration of  orange-juice. 

Lime-juice  was  early  found  to  be  a  preventive  of  scurvy, 
and  its  introduction  into  the  British  Navy  in  1795  led  to  the 
disappearance  of  the  disease  among  the  sailors. 

Hoist2  describes  how  Cartier  on  his  second  voyage  to 
Newfoundland,  in  1535,  administered  with  great  success  a 
fresh  decoction  of  pine  needles  to  a  crew  of  103  men  of 
whom  only  3  were  free  from  scurvy.  When  the  Eskimos  suffer 
from  this  disease  Hoist  states  that  they  turn  to  the  liver  of 
seals  or,  better,  to  fresh  "matok,"  which  is  the  rete  Malpighii 
of  the  skin  of  whales. 

During  the  siege  of  Paris  scurvy7  broke  out  on  a  large 
scale  on  account  of  the  prolonged  one-sided  diet  of  farinaceous 
nutriment.  Under  ordinary  conditions  in  civilized  commu- 
nities scurvy  is  of  rare  occurrence,  although  it  has  been  known 

1  Hess,  A.  F.:  "Proceedings  of  the  Society  for  Experimental  Biology  and 
Medicine,"  191 5,  xiii,  50. 

2  Hoist:  "XVth  International  Congress  of  Hygiene,"  Washington,  191 2,  ii, 
588. 


366  SCIENCE   OF   NUTRITION 

to  develop  in  poorhouses  which  have  been  placed  under 
ignorant  or  dishonest  control. 

Another  disease  which,  in  all  probability,  is  a  deficiency 
disease,  is  pellagra.  Funk1  states  that  in  the  United  States 
between  1907  and  191 2  20,000  persons  died  of  pellagra,  the 
mortality  being  40  per  cent,  among  those  suffering  from  the 
disease.  Pellagra  occurs  in  the  "corn  belt"  of  the  United 
States,  and  especially  among  the  poorer  classes  of  the  South. 
The  disease  has  developed  since  the  introduction  in  1880  of 
highly  perfected  machinery  which  furnishes  corn  and  wheat 
completely  freed  of  their  outer  coverings.  In  Italy,  where  the 
process  of  milling  corn  is  primitive,  the  mortality  among  the 
pellagrins  is  only  4  per  cent.  Nightingale2  reports  that  in  a 
prison  in  Rhodesia,  where  hand-milled  maize  was  given,  this 
food  proved  to  be  adequate,  but  when  maize  without  its  skin 
was  substituted  12 10  cases  of  pellagra  occurred.  There  is 
no  pellagra  in  zones  where  the  potato  is  cultivated.  Night- 
ingale concluded  that  the  disease  was  in  no  way  infectious  or 
contagious.  Green  vegetables,  meat,  butter,  and  potatoes 
are  found  to  be  the  best  antidotes. 

Goldberger3  reports  that  at  an  isolated  convict  camp  in 
Mississippi  11  volunteers  were  placed  on  a  one-sided  diet 
of  wheat,  corn,  and  rice,  as  the  result  of  which  6  individuals 
developed  pellagra  after  the  diet  had  been  administered  for 
about  five  months. 

Vedder4  believes  that  pellagra,  like  beriberi  and  scurvy,  is 
a  deficiency  disease,  though  the  possibility  of  its  being  of  in- 
fectious nature  remains  an  open  question.  The  deficiency  is 
attributed  to  a  too  exclusive  use  of  wheat  flour  in  association 
with  cornmeal,  salt  meats,  canned  goods,  all  of  which  are 
deficient  in  vitamins.  He  writes:  "If  pellagra  is  a  deficiency 
disease  it  has  an  extremely  long  depletion  period.     If  Gold- 

1  Funk:   "Munchener  medizinische  Wochenschrift,"  1914,  lxi,  698. 

2  Nightingale :   "British  Medical  Journal,"  1914,  No.  1,  300. 

8  Goldberger:    "Journal  of  the  American  Medical  Association,"  1916,   lxvi, 

47i- 

4  Vedder,  E.  B.:  "Archives  of  Internal  Medicine,"  1916,  xvm,  137;  Jour- 
nal of  the  Amer.  Med.  Assoc,"  1916,  lxvii,  1494. 


NUTRITIVE  VALUE  OF  MATERIALS  USED  AS  FOODS   367 

berger  and  his  associates  produced  pellagra  in  their  human 
feeding  experiments,  the  depletion  periods  on  the  diets  used 
may  be  placed  at  at  least  live  months." 

The  United  States  Public  Health  Service  has  maintained 
an  important  station  at  Spartanburg,  S.  C,  in  the  heart  of 
the  pellagra  district,  and  has  issued  several  valuable  reports 
which  cannot  here  be  detailed.1 

One  may  now  pass  to  the  more  detailed  consideration  of 
the  vitamins,  the  acknowledged  discoverer  of  which  is  Gow- 
land  Hopkins.  An  important  advance  was  scored  when 
Funk2  separated  a  material  from  yeast  a  few  milligrams  of 
which  cured  polyneuritis  in  pigeons.  From  ioo  kilograms  of 
dry  yeast  he3  extracted  2.5  grams  of  a  material  which,  when 
administered  in  doses  of  2  milligrams  to  pigeons  paralyzed 
with  beriberi  induced  by  a  diet  of  polished  rice,  cured  them 
in  three  hours. 

Working  in  Japan,  Suzuki,  Shimamura,  and  Odake4 
extracted  rice-bran  first  with  ether  and  then  with  alcohol. 
The  purified  substance  obtained  from  the  alcohol  extract  was 
said  to  cure  beriberi  in  pigeons  when  10  milligrams  of  the 
material  were  administered. 

The  effect  of  the  vitamins  upon  growth  has  been  espe- 
cially studied  by  Osborne  and  Mendel  and  by  McCollum  and 
Davis.  Whether  there  are  specific  vitamins  for  growth  has 
not  been  clearly  established. 

Experiments  concerning  growth  may  be  conducted  with 
especial  ease  upon  pigs  and  rats.  McCollum5  concludes  that 
the  growth  impulse  of  the  pig  is  greater  than  that  of  the  rat 
-on  account  of  the  data  contained  in  the  following  table : 

1  Hunter,  Givens,  and  Lewis:  "Preliminary  Observations  of  Metabolism 
in  Pellagra,"  Hygienic  Laboratory,  Bulletin  102,  1916;  Koch  and  Voegtlin, 
"Chemical  Changes  in  the  Central  Nervous  System  as  a  Result  of  Restricted 
Vegetable  Diet,"  Hygienic  Laboratory,  Bulletin  103,  1916. 

2  Funk:    "Journal  of  Physiology,"  1911-12,  xliii,  395. 

3  Funk:    Ibid.,  1913,  xlvi,  173;   ibid.,  1914,  xlviii,  228. 

4  Suzuki,  Shimamura,  and  Odake:  "Biochemische  Zeitschrift,"  1912, 
xliii,  89. 

6  McCollum:    "Journal  of  Biological  Chemistry,"  1914,  xix,  323. 


368  SCIENCE   OF   NUTRITION 


Weight  at  280  Days 

At 

Birth. 

Age  = 

Weight, 

280  Days. 

Weight 

at  Birth. 

Weight, 

Body  N, 

Body  N, 

Body 

Body 

Grams. 

Grams. 

Grams. 

Grams. 

Weight. 

N. 

Rat 

4-83 

O.064 

280 

8-5 

55 

133 

Pig 

1 1.9 

136,000 

2407. 

I50 

202 

It  is  evident  that  the  pig,  both  as  regards  body  weight 
and  nitrogen  content,  increases  relatively  somewhat  more 
rapidly  than  does  the  rat.  However,  in  both  species  the 
growth  impulse  is  very  great  and  very  constant,  so  that  de- 
viations in  the  curve  of  normal  growth,  when  caused  by 
insufficiency  of  diet,  may  be  readily  established.  The  rat 
reaches  full  growth  after  two  hundred  and  eighty  days  and 
lives  about  three  years. 

In  191 1  Osborne  and  Mendel1  published  the  first  results 
of  a  prolonged  series  of  valuable  contributions  to  the  knowl- 
edge of  growth.  These  authors  found  that  if  a  single  pro- 
tein, like  casein,  were  added  to  a  diet  made  up  of  starch, 
lard,  agar,  and  "protein-free  milk,"  such  a  diet  became 
adequate  for  the  growth  of  rats  during  the  first  two  months 
of  their  lives.  This  is  because  it  contains  "water-soluble" 
vitamins.  The  "protein-free  milk"  contains  0.7  per  cent, 
of  nitrogen,  80  per  cent,  of  lactose,  and  15  per  cent,  of 
inorganic  salts,  and  Osborne  and  Mendel2  estimate  that 
2.2  per  cent,  of  milk  protein  is  present.  This  makes 
0.6  per  cent,  of  the  weight  of  the  whole  diet,  or  3  per 
cent,  of  the  total  quantity  of  protein  ingested  when  an 
isolated  protein,  like  casein,  is  added  to  the  food  in  such 
measure  as  to  make  the  diet  contain  18  per  cent,  of  casein. 
In  later  work  Osborne  and  Mendel  state  that  the  "protein- 
free  milk"  introduces  protein  only  to  the  extent  of  0.13  per 
cent,  of  the  food  given. 

Hopkins3  showed  that  a  synthetic  food,  consisting  of 
protein,  carbohydrate,  lard,  and  the  proper  salts,  became  an 

Osborne  and  Mendel:  "Feeding  Experiments  with  Isolated  Food-sub- 
stances, Parts  I  and  II,"  Carnegie  Institution,  191 1,  Publication  156. 

2  Osborne  and  Mendel:  "Zeitschrift  fur  physiologische  Chemie,"  1912, 
lxxx,  316. 

3  Hopkins,  F.  G.:   "Journal  of  Physiology,"  191 2,  xliv,  425. 


NUTRITIVE    VALUE    OF   MATERIALS   USED   AS   FOODS      369 

entirely  satisfactory  diet  for  growing  rats  if  only  2  c.c.  of 
milk  were  given  also.  The  milk  was  administered  before 
the  rest  of  the  diet  in  order  to  prove  that  it  was  not  a  lack  of 
palatability  in  the  synthetic  food  which  was  the  cause  of  the 
failure  of  the  rats  to  grow.  Hopkins  also  made  the  very  sig- 
nificant discovery  that  an  alcoholic  extract  of  milk  solids  or 
of  yeast,  when  added  to  the  synthetic  diet  "in  astonishingly 
small  amounts,"  caused  normal  growth.  Though  the  syn- 
thetic diet  contained  plenty  of  calories  (see  p.  414)  growth 
took  place  only  when  the  accessory  substances  were  admin- 
istered. 

McCollum  and  Davis1  reported  that,  although  young  rats 
grew  for  sixty  or  ninety  days  on  such  diets  as  have  been 
described,  yet  after  this  time  growth  suddenly  stopped.  It 
could  be  re-established  if  butter  fat  or  the  ether  extract  of 
egg-yolk  was  added  to  the  diet.  Apparently,  the  organism 
runs  out  of  some  organic  complex  which  is  indispensible  to 
normal  growth  and  without  which  maintenance  in  good  con- 
dition is  impossible. 

Osborne  and  Mendel2  independently  reached  the  same 
results.  There  was  a  primary  growth  when  a  synthetic 
diet  which  included  lard  and  "protein-free  milk"  was  given, 
followed  by  failure  to  grow.  If  the  lard  were  replaced  by 
butter  or  egg-yolk  or  cod-liver  oil,  growth  was  resumed,  but 
almond  oil  was  inefficient  in  this  regard.  In  connection  with 
the  high  efficacy  of  cod-liver  oil  in  promoting  growth,  Osborne 
and  Mendel  refer  to  its  "popular  yet  inexplicable  reputation 
for  unique  nutritive  potency."  Beef  fat  was  found  to  be 
more  valuable  than  lard. 

McCollum  and  Davis3  show  that  olive  oil  and  cotton-seed 
oil,  like  almond  oil  and  lard,  cannot  be  used  to  foster  growth, 
whereas  the  fat  of  cod  testicle  and  pig's  kidney  are  very 
efficient.  Curiously  enough,  the  fat  of  the  pig's  heart  is  not 
of  value  in  producing  growth.     Animal  fats  and  especially 

1  McCollum  and  Davis:    "Journal  of  Biological  Chemistry,"  1913,  xv,  167. 

2  Osborne  and  Mendel:  Loc.  cit.,  1913,  xv,  311;  xvi,  423;  1914,  xvii,  401. 

3  McCollum  and  Davis:   Loc.  cit.,  1914,  xix,  245;  1915,  xx,  641;  xxi,  179. 

24 


370  SCIENCE   OF   NUTRITION 

milk  fats  have,  therefore,  nutrient  virtues  not  expressed  in 
calories. 

McCollum  and  Davis1  have  given  to  rats  a  standard 
diet  without  any  fat  in  it  and  have  brought  them  after  twenty 
to  twenty-five  weeks  to  the  threshold  of  death.  Then  on 
giving  the  standard  diet  with  an  equal  quantity  of  different 
grains  the  following  results  were  observed: 

Cornmeal,  Surprising  recovery  and  growth. 

Wheat  embryo,  Recovery  and  growth. 

Entire  wheat  kernel,  Recovery,  no  growth. 

Rye,  Little  or  no  improvement. 

Oats,  Little  or  no  improvement. 

The  authors  remark  that  such  results  illustrate  the  paucity 
of  our  knowledge  regarding  the  special  nutritive  value  of  the 
common  cereals. 

Finally  McCollum  and  Davis2  describe  how,  if  casein  be 
dialyzed  against  water  and  acetic  acid  so  that  all  the  salts  are 
washed  out,  this  product  when  given  with  butter,  dextrin, 
and  salts  causes  no  growth  in  rats. 

For  a  more  complete  discussion  the  reader  is  referred  to 
other  sources.3  One  may,  however,  summarize  the  work  upon 
the  influence  which  the  ingestion  of  purified  food-stuffs  has 
upon  growth,  as  follows: 

Purified  protein  +  carbohydrate    +  vegetable  fat 

-j-  inorganic  salts  =  no  growth. 

Purified  protein  +  carbohydrate    +  butter  fat 

+  inorganic  salts  =  no  growth. 

Purified  protein  +  carbohydrate    -f-  vegetable  fat 

+  inorganic  salts  +  vitamins*  =  no  growth. 

Purified  protein  +  carbohydrate    +  butter  fat 

+  inorganic  salts  +  vitamins*  =  growth. 

*  Water  or  alcohol  extract  of  peas,  rice  polishings,  wheat,  yeast,  or  "pro- 
tein-free milk,"  which  are  able  to  cure  polyneuritis  in  a  pigeon  in  a  few  hours. 

1  McCollum  and  Davis:   "Journal  of  Biological  Chemistry,"  1915,  xxi,  179. 

2  McCollum  and  Davis:   Ibid.,  1915,  xxiii,  231. 

3  Mendel:  "Journal  of  the  American  Medical  Association,"  1915,  lxiv, 
1539;  McCollum:    "New  York  Medical  Journal,"  1916,  ciii,  838. 


NUTRITIVE   VALUE    OF   MATERIALS    USED   AS   FOODS      371 

The  value  of  the  water-soluble  and  the  fat-soluble  vita- 
mins is  apparent. 

Since  the  purified  protein  may  be  given  free  from  phos- 
phorus without  prejudice  to  the  capacity  to  grow,  it  is  evi- 
dent that  an  animal,  when  fed  with  a  diet  of  pure  protein, 
carbohydrate,  fat,  and  simple  inorganic  salts,  may  produce 
synthetically  lecithin,  phosphatids,  nuclear  material  (purins, 
etc.),  hemoglobin,  and  bone-tissue.  McCollum  states  that  he 
has  never  seen  growth  enhanced  by  the  addition  of  organic 
phosphorus  to  a  diet.  Certain  amino-acids,  however,  must  be 
furnished  preformed.  Mendel  and  Osborne  and  McCollum 
and  Davis  are  in  essential  accord  with  regard  to  these  under- 
lying principles,  and  science  owes  them  much  for  their  labo- 
rious and  painstaking  contributions  to  this  long  obscure 
chapter  of  dietetics. 

In  another  chapter  of  this  book  (see  p.  156)  the  unequal 
nutritional  value  of  the  proteins,  such  as  are  found  in  meat  or 
gelatin,  have  been  emphasized.  This  difference  in  nutritive 
value  was  set  forth  by  Karl  Thomas,1  who  took  starch  and 
sugar  in  large  quantity  in  his  diet,  determined  the  minimal 
loss  of  body  protein  under  these  circumstances,  and  then 
added  to  the  diet  food  materials  containing  different  pro- 
teins, in  order  to  determine  their  relative  power  in  sparing 
the  body  from  a  loss  of  tissue  protein.  The  values  given 
below  Thomas  named  the  biologic  values  of  the  proteins 
employed : 

BIOLOGIC  VALUES  OF  DIFFERENT  PROTEINS,  AS  MEASURED 
BY  THE  PERCENTAGE  QUANTITY  OF  BODY  PROTEIN  WHICH 
THEIR  INGESTION  WILL  SPARE  FROM  LOSS 

Ox  meat 104       Cherry-juice 79 

Cows'  milk 100       Yeast 71 

Fish 95       Casein 70 

Rice 88       Nutrose 69 

Cauliflower 84       Spinach 64 

Crab  meat 79       Peas 56 

Potatoes 79       Wheat  flour 40 

Cornmeal 30 

1  Thomas,  K.:   "Archiv  fur  Physiologie,"  1909,  p.  219. 


372  SCIENCE   OF   NUTRITION 

These  excellent  experiments  show  clearly  the  superior 
value  of  meat,  fish,  and  milk  proteins  as  conservers  of  body 
protein  when  contrasted  with  the  ordinary  group  of  vegetable 
proteins. 

The  reason  for  this  biologic  difference  lies  in  the  amino- 
acid  content  of  the  different  proteins,  as  has  been  beautifully 
shown  in  experiments  with  growing  animals.  Willcock  and 
Hopkins1  were  the  pioneers  in  this  field.  They  prepared  a 
diet  in  which  casein  was  the  sole  nitrogenous  constituent 
and  obtained  good  growth  in  mice  when  this  diet  was  ad- 
ministered to  them.  When  zein,  the  principal  protein  of  corn, 
was  substituted  for  casein  in  the  diet,  the  animals  declined 
and  died  in  about  seventeen  days.  Addition  of  tyrosin, 
which  zein  contains  in  plentiful  amount,  was  without 
effect  upon  the  length  of  life.  When,  however,  trypto- 
phan, which,  as  well  as  lysin  and  glycocoll,  is  absent  from 
the  zein  molecule,  was  added  to  the  diet  in  an  amount 
equal  to  2  per  cent,  of  the  total  zein  given,  the  animals 
lived  thirty-two  days.  Hopkins  suggests  the  possibility  that 
in  the  absence  of  tryptophan  epinephrin  cannot  be  formed 
and  collapse  follows.  Osborne  and  Mendel2  have  maintained 
a  rat  at  an  almost  constant  body  weight  of  50  grams  for  one 
hundred  and  eighty-two  days  on  a  food  containing  zein  as 
its  dominant  protein,  with  the  addition  of  tryptophan  equal  to 
3  per  cent,  of  the  zein.  Since  zein  is  free  from  the  amino-acid 
lysin,  it  seemed  possible  that  normal  growth  might  be  ob- 
tained when  the  protein  in  the  dietary  consisted  of  zein  supple- 
mented by  tryptophan  and  lysin;  such,  indeed,  proved  to 
be  the  case  (Fig.  22). 

A  striking  detail  of  this  work  is  that  at  the  beginning  of 
the  experiment  a  patch  of  hair  on  the  animal's  back  was  dyed 
red  and  this  color  remained  unchanged  for  six  months.  When 
lysin  was  added  to  the  diet  and  growth  was  resumed  the  color 
soon  disappeared.    New  growth  became  possible  in  the  hairs 

1  Willcock  and  Hopkins:    "Journal  of  Physiology,"  1906-7,  xxxv,  88. 

2  Osborne  and  Mendel:   "Journal  of  Biological  Chemistry,"  1915,  xx,  351. 


NUTRITIVE   VALUE    OF   MATERIALS   USED   AS   FOODS      373 

as  in  other  parts  of  the  body.  The  addition  of  lysin  alone  to 
a  dietary  containing  zein  does  not  prevent  the  decline  which 
always  accompanies  the  partak- 
ing of  a  diet  which  is  free  from 
tryptophan. 

From  the  experiments  of 
McCollum,1  one  may  calculate 
that  gelatin  (which  lacks  tyro- 
sin,  tryptophan,  and  cystin) 
when  given  with  starch  to  a  pig 
in  such  quantity  that  the  gela- 
tin is  the  equivalent  of  the 
"wear-and-tear"  quota  of  pro- 
tein metabolism  body  protein 
is  protected  from  waste  to  an 
extent  of  39  per  cent,  (see  p. 
283).  When  zein  is  adminis- 
tered under  similar  conditions 
body  protein  is  spared  to  an 
extent  of  73  per  cent.,  thus 
demonstrating  the  superiority 
of  zein  to  gelatin  in  this  re- 
gard. 

The  study  of  the  failure  of 
zein  to  produce  growth  or  to 
prevent  decline  brings  up  the 
question  as  to  the  nutritive 
value  of  maize.  Osborne  and 
Mendel2  state  that  zein  and 
glutelin  form  72  per  cent,  of  the 
proteins  of  the  maize  kernel. 
Glutelin,  which  is  present  in 
about  one-half  the  quantity  of 
that  of  zein,  is  a  complete  protein,  containing  all  the  familiar 


1  McCollum,  E.  V.:   "American  Journal  of  Physiology,"  1011-12,  xxix,  215. 

2  Osborne  and  Mendel:    "Journal  of  Biological  Chemistry,"  1914,  xviii,  1. 


374 


SCIENCE    OF   NUTRITION 


amino-acids,  and  is  efficient  in  producing  growth,  but  there 
is  not  enough  of  this  higher  quality  protein  to  produce  more 
than  moderate  growth.  A  small  addition  of  a  protein  like 
lactalbumin,  however,  to  a  diet  containing  maize  protein  at 
once  induced  normal  growth. 

The  corn  grain  contains  'little  calcium,  and  the  daily  addi- 
tion of  2.5  grams  to  the  diet  of  a  corn-fed  pregnant  sow  very 
favorably  influences  the  condition  of  the  offspring.1 

Hart  and  McCollum2  noticed  that  when  swine  are  re- 
stricted to  cornmeal  and  corn-gluten  feed  there  is  little  or  no 
growth,  but  when  salts  are  added,  so  that  the  salt  content  of 
the  ration  approximates  that  of  milk,  good  growth  follows. 
The  desire  for  salts  may  explain  the  "rooting"  of  the  hog. 
The  desirability  of  a  milk  addition  to  the  diet  of  the  growing 
hog  is  emphasized  in  the  following  experiment,  which  shows 
the  higher  biologic  value  of  the  milk  proteins  as  contrasted 
with  vegetable  proteins.     (See  also  p.  371.) 

EFFECT   OF  THE   KIND   OF  PROTEIN  UPON  THE   AMOUNT  OF 
PROTEIN   RETAINED   FOR   GROWTH 


Source  of  Protein. 


Corn 

Wheat 

Oats 

^  corn  +  I  wheat  +  3  oats 

Wheat  embryo  4-  wheat  gluten. 

Casein 

Skim  milk 


Calories  Per 
Kg.  in  Ration. 


109 
i°3 
94 
98 
98 
102 
94 


Protein  in  Per 
Cent,  in 
Ration. 


10.5 
11.0 

14-5 
12.3 

57-9 
16.5 
15-5 


Protein  Re- 
tained for 
Growth  in 
Per  Cent. 


23 
26 
21 
46 
63 


When  vegetable  protein  was  administered  in  large  quan- 
tity there  was  about  the  same  percentage  retention  as  when 
it  was  given  in  smaller  amount.  Hence,  McCollum  con- 
cludes that  the  limitation  of  growth  when  vegetable  proteins 


1  Evvard,  Dox,  and  Guernsey:    "American  Journal  of  Physiology,"  1914, 
xxxiv,  312. 

2  Hart  and  McCollum:    "Journal  of  Biological  Chemistry,"  1914,  xix,  373. 
Consult  also  Hogan:  Ibid.,  1916,  xxvii,  193. 


NUTRITIVE    VALUE    OF    MATERIALS    USED    AS    FOODS      375 

are  taken  alone  is  due  to  the  chemical  make-up  of  these 
proteins  and  not  to  any  diminution  in  the  animal's  power  to 
grow. 

The  work  of  Osborne  and  Mendel  upon  the  subject  of  the 
behavior  of  gliadin,  one  of  the  principal  proteins  derived  from 
wheat,  has  been  of  very  great  interest.  Gliadin  is  a  protein 
which  yields  44  per  cent,  of  glutamic  acid  and  13  per  cent, 
of  prolin,  these  being  present  in  exceptionally  large  quanti- 
ties. On  the  other  hand,  it  contains  only  0.92  per  cent,  of 
lysin  and  very  little  arginin  and  histidin.  When  gliadin  is 
the  only  protein  in  the  diet  grown  rats  may  be  maintained 
over  long  periods  (546  days),  but  ungrown  rats  fail  to  grow,1 
although  the  gliadin  administered  is  completely  digested  and 
absorbed.  The  animals  remain  stunted  and  resume  growth 
only  when  an  adequate  protein  in  the  diet  is  offered  to  them. 
Osborne  and  Mendel2  have  stunted  albino  rats  until  they 
were  550  days  old,  and  then  by  a  change  of  diet  observed  a 
resumption  and  completion  of  growth,  although  ordinarily 
such  completion  of  growth  is  accomplished  before  the  age  of 
300  days.  It  appears  that  if  in  these  animals  the  function  of 
growth  has  not  been  fulfilled  at  the  usual  period  of  life  the 
capacity  to  grow  is  never  lost. 

If  a  diet  be  made  up  which  contains  gliadin  as  the  dominant 
protein,  and  lysin  be  added  sO  that  the  protein  quota  contains 
2  or  3  per  cent,  of  lysin,  normal  growth  is  resumed  by  a  rat 
which  had  been  stunted  through  the  influence  of  the  diet  poor 
in  lysin.3 

The  principal  proteins  existing  in  wheat  are  gliadin  and 
wheat  glutenin,  there  being  equal  amounts  of  each.  Since 
the  latter  form  of  protein  completely  suffices  for  the  growth 
of  rats,  it  is  evident  that  the  value  of  wheat  protein  is  greatly 
enhanced  by  the  presence  of  this  constituent. 

A  notable  contribution  to  the  knowledge  of  the  relative 
value   of    lactalbumin    and    casein   has   been    presented   by 

1  Osborne  and  Mendel:    "Journal  of  Biological  Chemistry,"  191 2,  xii,  473. 

2  Osborne  and  Mendel:    Ibid.,  1915,  xxiii,  439. 

3  Osborne  and  Mendel:   Ibid.,  1916,  xxv,  1. 


376 


SCIENCE    OF   NUTRITION 


Osborne  and  Mendel.1     It  will  be  remembered  that  Thomas 
found  that  casein  was  inferior  to  milk  protein  for  the  main- 


AVDQfj    W>  80 


iv  ~vi/uyj    "^  v';  ,w"  •*■*  "v  "^  ,u"  *-w  **■"  -^~ 

Fig.  23. — Comparison  of  growth  on  diets  containing  approximately  the 
same  percentage  (4.5  per  cent.)  of  different  proteins,  namely,  ladalbumin, 
edestin,  casein,  globulin  (squash-seed),  and  glycmin  (soy  bean). 

tenance  of  nitrogen  equilibrium  in  man.     The  cause  of  the 


1  Osborne  and  Mendel:  "Journal  of  Biological  Chemistry,"  1915,  xx,  351; 
1916,  xxvi,  1. 


NUTRITIVE   VALUE    OF   MATERIALS   USED   AS   FOODS      377 

inferiority  of  casein  is  largely  due  to  the  fact  that  it  contains 
only  0.6  per  cent,  of  cystin  (Fig.  23). 

When  3  per  cent,  of  this  latter  amino-acid  is  added  to  the 
casein  content  of  a  diet,  Mendel  and  Osborne  found  that 
growth  in  the  rat  was  accomplished  with  a  much  smaller 
quantity  of  protein  than  when  casein  alone  was  given.  These 
results  are  presented  in  the  following  table: 

INFLUENCE   OF  THE  AMOUNT   OF   DIFFERENT   VARIETIES   OF 
MILK  PROTEIN  UPON  THE  GROWTH  OF  RATS 


Percentage  of 

Protein  in  the 

Diet. 

Casein. 

Casein  +  3  Per  Cent. 
Cy  stein. 

Lactalbumin. 

18 

Normal. 

Normal. 

15 

Normal. 

Normal. 

12 

Little   below   nor- 
mal. 

Normal. 

9 

Limited. 

Normal. 

Normal. 

6 

Slight. 

Good. 

4§ 

Maintenance. 

Slight. 

Limited. 

2 

Decline. 

Maintenance. 

1 

Decline. 

It  is  evident  that  a  diet  containing  15  per  cent,  of  casein 
may  be  given  to  rats  and  produce  normal  growth,  whereas 
when  12  per  cent,  is  present  normal  growth  does  not  take 
place.  The  addition  of  3  per  cent,  of  cystein  to  casein  so 
that  this  mixture  forms  9  per  cent,  of  the  diet  yields  a  food 
capable  of  supporting  normal  growth.  There  is  greater 
value  in  lactalbumin  in  promoting  growth  than  in  casein 
because  the  amino-acids  are  arranged  in  more  suitable  pro- 
portions. The  protein  of  whey  appears  to  be  as  perfect  a  ma- 
terial for  use  in  the  service  of  growth  as  any  protein  known. 

The  following  table,  which  is  arranged  from  data  given  by 
Mendel,1  presents  the  proteins  with  a  supply  of  which  an 
organism  may  grow,  and  also  those  which,  if  fed,  do  not  pro- 
duce growth  of  the  organism: 

1  Mendel:  Harvey  Society  Lecture,  "Journal  of  the  American  Medical 
Association,"  1915,  lxiv,  1539. 


378  SCIENCE    OF   NUTRITION 

VALUE  OF   PROTEINS   IN  THE   FUNCTION  OF   GROWTH 
Allow  Growth.  Failure  to  Grow. 

Casein milk.  Legumelin soy  bean. 

Lactalbumin milk.  Vignin vetch. 

Ovalbumin hen's  egg.  Gliadin wheat  or  rye. 

Ovovitellin hen's  egg.  Legumin pea. 

Edestin hemp-seed.  Legumin vetch. 

Globulin squash-seed.  Hordein barley. 

Excelsin Brazil-nut.  Conglutin lupin. 

Glutelin maize.  Gelatin horn. 

Globulin cotton-seed.  Zein maize. 

Glutenin wheat.  Phaseolin white  kidney  bean. 

Glycinin soy  bean. 

Cannabin hemp-seed. 

It  is  evident  from  the  material  presented  in  this  chapter 
that  the  science  of  nutrition  includes  something  more  than 
the  production  of  energy  from  fat,  carbohydrate,  and  protein. 
There  must  be  certain  salts  and  certain  qualities  of  protein 
in  the  diet,  and  there  must  be  minute  amounts  of  "vitamins." 
The  chemical  composition  of  the  latter  will  some  day  be 
known,1  even  as  the  chemical  composition  of  epinephrin  is 
known.  Epinephrin,  an  essential  of  life,  is  present  in  the 
blood  to  the  extent  of  i  part  in  100,000,000.  In  like  manner, 
vitamins  which  are  present  in  meat,  milk,  fresh  green  vege- 
tables, and  grains  are  essential  to  the  harmonious  correlation 
of  the  nutritive  functions  of  animals.  Lafayette  Mendel 
first  suggested  the  use  of  the  word  "hormone"  in  connection 
with  the  vitamins.  Gowland  Hopkins  adopts  the  term  "exog- 
enous hormones."  The  expression  "food  hormones"  would 
also  be  exactly  descriptive  of  the  nature  of  these  substances. 

1  Williams  and  Seidell  ("Journal  of  Biological  Chemistry,"  1016,  xxvi,  431) 
have  separated  from  the  filtrate  of  autolyzed  yeast  a  crystalline  antineuritic 
substance  which,  on  recrystallization,  lost  its  antineuritic  properties  and  was 
converted  into  adenin.  The  authors  suggest  that  an  isomer  of  adenin  is  the 
chemical  entity  responsible  for  the  physiologic  properties  of  the  vitamin  of 
yeast.     They  are  continuing  this  inquiry. 


CHAPTER  XIV 

THE   FOOD    REQUIREMENT   DURING   THE   PERIOD 
OF  GROWTH 

"Mute  and  still,  by  night  and  by  day,  labor  goes  on  in 
the  workshops  of  life.  Here  an  animal  grows,  there  a  plant. 
The  wonder  of  the  work  is  not  less  in  the  smallest  being  than 
in  the  largest."1 

In  the  last  chapter  the  average  food  requirement  of  a 
normal  adult  organism  was  discussed.  This  diet,  however, 
may  be  exceeded  in  cases  where  there  is  a  renewal  of  tissue 
following  wasting  disease,  or  where  there  is  a  development 
of  new  tissue,  as  during  pregnancy,  or  afterward  during  lac- 
tation, which  involves  the  growth  of  the  newborn  infant. 

Tangl2  has  reported  some  interesting  observations  on  the 
heat  production  which  takes  place  in  the  hen's  egg  incubated 
at  380  and  30°  F.  Tangl  called  this  the  "energy  for  develop- 
ment" or  the  "ontogenetic  energy."  His  method  was  to  de- 
termine the  calories  in  fresh  laid  eggs  and  to  compare  that 
amount  with  the  calories  found  within  the  egg-shell  at  the 
moment  of  the  birth  of  the  chick.  In  this  latter  case  the  chick 
and  the  balance  of  egg-yolk  were  determined  separately. 

The  results  of  these  experiments  showed  that  for  the  de- 
velopment of  1  gram  of  chick  658  small  calories  were  used,  or 
for  the  production  of  1  gram  of  solids  contained  in  a  new- 
born chick  3425  small  calories  were  required. 

Farkas3  has  since  shown  that  for  the  development  from  the 
egg  of  1  gram  of  silkworm  larvas  882  small  calories  are  re- 
quired, or  for  1  gram  of  dry  solids,  3125  small  calories,  figures 
which  he  compares  with  Tangl's  for  the  egg. 

1  Rubner:  "Verhandlungen  der  Ges.  der  Naturforscher  und  Arzte,"  1908, 
P-  77- 

2  Tangl:    "Pfluger's  Archiv,"  1903,  xciii,  327. 

3  Farkas:   Ibid.,  1903,  xcviii,  490. 

379 


380  SCIENCE    OF   NUTRITION 

When  the  whole  hen's  egg  is  considered,  Tangl  finds  that 
$2  calories  or  35  per  cent,  of  the  amount  of  chemical  energy 
in  the  original  egg  is  deposited  in  the  body  of  the  young  em- 
bryo. The  energy  of  development  used  in  the  production  of 
the  young  chick  amounts  to  16  calories  or  17  per  cent,  of  the 
original  total.  The  balance,  44  calories  or  48  per  cent,  of 
the  original  energy  in  the  egg,  is  largely  found  in  the  abdomen 
of  the  chick  and  is  absorbed  by  the  animal  during  the  early 
days  of  life. 

It  is  apparent  from  the  above  that  approximately  one- 
sixth  of  the  energy  in  a  hen's  egg  is  used  in  the  development 
of  a  chick  whose  body  contains  one-third  the  original  energy 
of  the  egg.  The  other  half  of  the  energy  becomes  available 
for  the  chick  during  the  first  days  of  its  separate  life  through 
absorption  from  the  intestinal  wall. 

Tangl  finds  that  each  egg  loses  in  solids  during  incuba- 
tion, and  that  the  heat  value  of  1  gram  of  such  solids  is  over 
9  calories.  Since  1  gram  of  fat  yields  9.3  calories,  the  natural 
inference  is  that  fat  furnishes  the  energy  for  development. 

Hasselbalch1  had  formerly  shown  that  the  respiration  car- 
ried on  by  an  egg  indicated  a  respiratory  quotient  amounting 
to  0.677.     This  low  quotient  points  to  the  combustion  of  fat. 

Tangl2  also  states  that  there  is  no  loss  of  protein  nitrogen 
by  the  egg  during  incubation,  and  that  the  egg-shell  con- 
tributes to  bone  formation  in  the  chick. 

Glaser3  has  found  that  the  energy  of  ontogenesis  for 
the  eggs  of  fundulus  is  similar  in  quantity  to  that  necessary 
for  the  hen's  egg  and  for  silkworm  larvae,  and  is  also  evolved 
at  the  expense  of  the  oxidation  of  fat.  He  reiterates  Tangl's 
statement  that  the  specific  energy  of  ontogenesis  is  not  a 
function  of  phylogenetic  position  or  of  organization,  but  that 
the  embryonic  construction  of  different  kinds  of  highly  organ- 
ized living  forms  may  take  place  at  the  same  expense  of 
chemical  energy. 

1  Hasselbalch:    "Skan.  Archiv  fur  Physiol.,"  1900,  x,  353. 

2  Tangl  and  Mituch:  "Pfluger's  Archiv,"  1908,  cxxi,  437;  Tangl:  Ibid.,  423. 

3  Glaser:   "Biochemische  Zeitschrift,"  1912,  xliv,  180. 


FOOD   REQUIREMENT   DURING   THE   PERIOD   OF   GROWTH       38 1 

There  is  no  change  in  the  intensity  of  the  oxidation 
processes  in  women  during  menstruation,  a  fact  first  shown  by 
L.  Zuntz1  and  confirmed  by  Du  Bois.2 

Schrader3  showed  that  there  was  a  retention  of  protein 
nitrogen  in  six  women  either  during  the  whole  menstrual 
period  or  during  the  first  part  of  it.  This  is  in  compensation 
.for  the  loss  of  blood. 

During  pregnancy  in  the  higher  animals  not  only  must 
there  be  growth  of  the  breasts,  of  the  uterine  musculature, 
and  of  the  embryo  itself,  but  there  must  be  energy  ex- 
pended in  maintaining  the  new  organism;  hence  the  appe- 
tite of  the  mother  increases  during  pregnancy.  Magnus- 
Levy4  finds  an  increased  requirement  for  oxygen  on  the  part 
of  the  mother  as  pregnancy  progresses.  His  table  is  as  fol- 
lows: 

Oxygen  in  C.C. 
per  Min. 

Non-pregnant 302 

Third  month  of  pregnancy 320 


Fourth 

Fifth 

Sixth 

Seventh 

Eighth 

Ninth 


325 

34o 
349 
348 
363 
383 


Rubner5  called  attention  to  the  fact  that  the  mammalian 
embryo  has  no  appreciable  weight  in  relation  to  the  mother 
until  the  middle  of  the  gestation  period,  and,  in  fact,  up  to 
this  time  the  metabolism  of  the  mother  is  usually  found  to  be 
unchanged.6  At  term,  however,  the  weight  of  the  child  is 
between  5  and  6  per  cent,  that  of  the  mother,  and  when  the 
various  adnexa  are  considered  the  mother  loses  during  par- 

1  Zuntz,  L.:   "Archiv  fur  Physiologie,"  1906,  p.  393. 

2  Gephart  and  Du  Bois:    "Archives  of  Internal  Medicine,"  1916,  xvii,  907. 

3  Schrader:     "Zeitschrift  fur  klinische  Medizin,"  1894,  xxv,  72. 

4  Magnus-Levy:  "Zeitschrift  fur  Geburtshiilfe  u.  Gynakologie,"  1904,  lii, 
116.  Also  see  Magnus-Levy:  von  Noorden's  "Handbuch  des  Stofhvechsels," 
1906,  i,  409. 

6  Rubner:   "Archiv  fur  Hygiene,"  1908,  lxvi,  177. 

6  Zuntz:  "Ergebnisse  der  Physiologie,"  1908,  vii,  430;  "Archiv  fiir  Gyna- 
kologie," 1910,  xc,  452. 


382 


SCIENCE   OF   NUTRITION 


turition  the  equivalent  of  20  per  cent,  of  her  postpartum 
weight. 

Experiments  which  were  carried  out  by  Carpenter  and 
Murlin1  present  an  admirable  picture  of  metabolism  under 
the  change  in  conditions  effected  by  parturition.  These 
authors  investigated  the  heat  production  of  three  pregnant 
women  in  the  "bed  calorimeter"  of  the  Carnegie  Nutrition 
Laboratory  and  followed  this  with  similar  determinations 
upon  the  same  women  after  parturition,  each  woman  being 
placed  in  the  calorimeter  several  times,  alone  and  also  with 
her  offspring.  Observations  were  made  during  one  to  three 
weeks  preceding  parturition  and  during  about  two  weeks  fol- 
lowing the  event. 

A  summary  of  the  results  is  presented  in  the  following 
table : 

METABOLISM  BEFORE  AND  AFTER  PARTURITION.  THE  MET- 
ABOLISM OF  THE  CHILD  WAS  DETERMINED  BY  DIFFER- 
ENCE 


Calories 

per  Kg. 

per  Hour. 


Case  I: 

Before  parturition 
After  parturition. 

Difference 

Child 

Case  II: 

Before  parturition 
After  parturition. 

Difference 

Child 

Case  III: 

Before  parturition 
After  parturition. . 

Difference 

Child 

Average : 

Before  parturition 
After  parturition. . 


Weight 
in  Kg. 

Calories 
per  Hour. 

Calories 

per  Sq.  M. 

(Meeh). 

63.0 

60.7 

31-4 

51-4 

53-9 

31-7 

11.6 

6.8 

2.7 

7-3 

30.5 

58.0 

64.7 

35-1 

48.5 

59-° 

36.2 

9-5 

5-7 

3-4 

9.8* 

34-9 

69.1 

70.6 

34-0 

60.1 

60.4 

31-9 

Q.O 

10.2 

3-2 

9-3 

34-8 

03-4 

65-3 

33-4 

53-3 

57-8 

33-2 

0.96 
1. 05 

2.70 


1. 11 

1. 21 


1.02 
1. 00 


2.90 


1 -°3 
1.09 


*  Child  cried  during  the  experiments. 
1  Carpenter  and  Murlin:    "Archives  of  Internal  Medicine,"  191 1,  vii,  li 


FOOD   REQUIREMENT   DURING   THE   PERIOD    OF   GROWTH       383 

In  cases  I  and  III  the  metabolism  of  the  child  alone  was 
almost  exactly  equal  to  the  decrease  of  the  metabolism  of  the 
woman  which  ensued  after, parturition.  The  authors  point 
out  that  during  parturition  the  mother  loses  a  considerable 
weight  of  material,  such  as  liquor  amnii,  blood,  membranes, 
placenta,  etc.,  which  themselves  participate  little  or  not  at 
all  in  the  production  of  heat.  In  the  cases  here  cited  the 
heat  production  of  the  newborn  infant  averages  2.6  times 
that  of  the  mother  when  the  calculation  is  based  upon  the 
calories  produced  per  kilogram  of  body  weight.  It  is  prob- 
able, though  not  experimentally  demonstrated,  that  the 
youthful,  growing  protoplasm  in  utero  is  also  endowed  with 
a  high  metabolism  per  kilogram  of  body  weight.  In  the  preg- 
nant condition  the  average  weight  of  these  three  women  was 
63  kilograms,  and  33.4  calories  were  produced  per  square 
meter  of  surface.  After  parturition  the  average  weight  was 
53  kilograms  and  the  heat  production  33.2  calories  per  square 
meter  of  surface.  Using  Meeh's  formula,  the  average  heat 
production  of  women  between  twenty  and  fifty  years  old,  as 
determined  by  Benedict  and  Emmes,1  is  32.3  calories  per 
square  meter  of  surface.  Herein  lies  a  most  remarkable  con- 
firmation of  the  "law  of  skin  area"  (see  p.  129).  Notwith- 
standing a  sudden  loss  of  10  kilograms,  or  nearly  20  per  cent, 
of  the  body  weight,  as  well  as  the  loss  of  tissues  with  very 
uneven  capacities  of  heat  production,  the  sum  total  of  energy 
production  is  not  altered  by  gestation  or  parturition  from 
the  common  standard  of  mammalian  metabolism  as  based 
upon  the  surface  area. 

The  three  mothers  nursed  their  children  throughout  the 
days  of  experimentation.  It  appears  that  lactation  does  not 
increase  the  heat  production.  This  is  not  strange,  since  the 
rearrangement  of  food  materials  in  the  preparation  of  milk 
depends  upon  hydrolytic  cleavages  and  syntheses  which  in- 
volve hardly  any  thermal  reactions,  and  also  because  it  is 

1  Benedict,  F.  G.,  and  Emmes,  L.  E.:  "Journal  of  Biological  Chemistry," 
1915,  xx,  253. 


384  SCIENCE    OF   NUTRITION 

known  also  that  the  secretory  activity  of  a  gland,  such  as  the 
kidney  when  it  eliminates  urea  or  sodium  chlorid  in  increased 
quantity,  has  no  influence  upon  the  total  heat  production  of 
the  body. 

The  findings  of  Hasselbalch1  are  not  essentially  different 
from  those  of  Carpenter  and  Murlin. 

The  composition  of  the  urine,  as  regards  its  various  con- 
stituents, is  scarcely  changed  in  pregnancy.  Thus,  Murlin 
and  Bailey2  found  that  the  output  of  ammonia  was  not  in- 
creased, that  the  relative  quantity  of  urea  decreased  because 
of  protein  retention,  and  that  the  quantity  of  oxidized  inor- 
ganic sulphur  also  decreased  for  the  same  reason,  retention 
for  protein  synthesis.  The  "creatinin  coefficient"  fell,  which 
the  authors  explain  as  being  due  to  the  addition  of  inert  mate- 
rial to  the  mother's  body. 

On  empirical  grounds  von  Winckel3  for  many  years  used 
the  following  diet  for  pregnant  women  with,  he  says,  "ex- 
cellent results": 

Protein 90  grams.  369  calories. 

Fat 27     "  251       " 

Carbohydrates 200     "  820       " 

Total 1440  calories. 

This  certainly  seems  a  very  low  ration  and  one  hardly  com- 
patible with  furnishing  the  full  calorific  requirement.  It  was 
employed  to  prevent  an  excessive  growth  of  the  child  within 
the  uterus. 

Murlin4  has  made  experiments  on  the  total  metabolism  in 
pregnant  dogs.  From  one  animal  a  single  puppy  was  born  as 
the  result  of  a  first  pregnancy  and  a  litter  of  five  from  a  later 
one.    The  following  results  were  obtained: 

1  Hasselbalch:  "Skan.  Archiv  fur  Physiologic,"  191 2,  xxvii,  1. 

2  Murlin  and  Bailey:   "Archives  of  Internal  Medicine,"  1913,  xii,  288. 

3  von  Winckel :  von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1904, 
ii,  469. 

4  Murlin:  Proceedings  of  the  American  Physiological  Society,  "American 
Journal  of  Physiology,"  1909,  xxiii,  p.  xxxii. 


FOOD   REQUIREMENT   DURING   THE   PERIOD   OF    GROWTH       385 


Day  from 
Parturition. 


Date. 


Third  before June  23 

First  after June  27 

Nineteenth  after..  .  .  July  15 

Third  before I  Dec.  11 

First  after Dec.  15 


Excreta. 

Calories 
or  Met- 

abolism. 

Total  N. 

Total  C. 

8.6 

59-4 

551-3 

8.4 

65-8 

640.6 

5-3 

51.6 

5°5-3 

6.8 

74-7 

764.9 

8-3 

100.6 

1058.8 

One  puppy  born. 
Weight,  280  grams. 
Sexual  rest. 
Five  puppies  born. 
Weight,  1560  gms. 


The  increase  of  metabolism  which  can  be  attributed  to  the 
pregnant  condition  may  be  found  by  subtracting  the  metabo- 
lism during  sexual  rest  from  that  observed  just  before  parturi- 
tion.    By  so  doing  the  following  figures  were  obtained: 

First  pregnancy,  551.3  —  505.3  =  46  calories  daily  for  one  puppy  of  280  grams. 
Second  pregnancy,  764.9  —  505.3   =   259.6  calories  daily  for  five  puppies  of 
1560  grams. 

This  extra  metabolism  was  proportional  to  the  weight  of 
the  puppies  at  birth.  In  the  case  of  the  first  pregnancy  the 
extra  metabolism  was  164,  and  in  the  second  165  calories  per 
kilogram  of  puppy  dog  delivered  three  days  later. 

It  is  interesting  to  note  that  the  mother  and  her  five  newly 
born  puppies  together  produced  twice  as  much  heat  as  did  the 
non-pregnant  mother  alone.  The  experiments  were  all  made 
at  a  temperature  of  between  270  and  280  C.  It  is  evident  that 
the  puppies  suckled  by  the  mother  and  exposed  to  the  outside 
temperature  had  a  larger  metabolism  than  they  had  had  in 
utero.  For  the  proper  maintenance  of  the  five  offspring  the 
mother  with  a  normal  metabolism  of  505  calories  would  have 
to  produce  milk  to  provide  for  a  metabolism  of  about  550 
calories  in  the  puppies,  and  still  more  to  furnish  material  for 
their  rapid  growth. 

Ostertag  and  Zuntz1  report  that  a  sow  may  yield  a  milk 
rich  in  fat  (12.9  per  cent.),  and  in  such  quantity  that  the  energy 


1  Ostertag  and  Zuntz:     "Landwirtsch.     Jahrbticher,"  1908,  xxsvii,  226. 


386 


SCIENCE    OF   NUTRITION 


content  may  amount  to  from  two-  to  fivefold  that  required  for 
the  mother  sow's  metabolism. 

An  extraordinary  phenomenon  which  has  been  observed 
in  dogs  and  rabbits  is  that  during  the  early  weeks  of  preg- 
nancy there  is  a  loss  of  nitrogen  from  the  mother's  body  even 
when  the  food  ingested  would  be  entirely  sufficient  to  main- 
tain nitrogen  equilibrium  under  usual  circumstances.1  Jager- 
roos  quotes  Ver  Ecke's  description  of  this  as  "the  sacrifice 
of  the  individual  for  the  good  of  the  species."  It  seems 
certain  that  the  development  of  the  fetus  is  accompanied  by 
the  destruction  of  the  maternal  protoplasm,  perhaps,  as 
Murlin  has  suggested,  in  order  to  afford  hereditary  building 
stones  for  the  laying  down  of  the  youthful  protoplasm  in 
accordance  with  the  type  characteristic  of  the  species. 

This  is  the  period  of  the  "morning  sickness,"  established 
in  pregnant  women  during  the  fourth  to  sixth  week,  and  ac- 
companied by  lack  of  appetite,  vomiting,  emaciation,  and 
usually  sallowness  of  face.  Dissimilation  of  tissue  and  gastro- 
intestinal disturbances  are  accompanying  phenomena. 

One  of  Murlin's2  experiments  covering  the  period  of  ges- 
tation in  a  dog  is  given  below: 


WEEKLY  NITROGEN  BALANCE  IN  A  PREGNANT  DOG 


Week. 

Calories  in 

Food  per 

Day. 

NlN 

Diet. 

N  IN 

Excreta. 

N  to 
Body. 

I 

II 

Ill 

IV 

V 

VI 

VII 

VIII 

IX* 

900 

976f 

976 

976 

976 

976 

976 

976 

976{ 

52.287 
56.063 
56.063 
56.063 
56.063 
56.063 
56.063 
56.063 
32.036 

63.116 
60.893 
62.031 
64.508 
62.594 
60.064 
54.262 
47.042 
25.867 

-8.83 
-4-83 
-5-97 
-8-44 
-6-53 
—  4.00 
+  1.80 

+  9-02 
+  6.25 

*  Four  days  only. 


f  69.7  calories  per  kilogram. 


t  61.0  calories  per  kilogram. 


1  Hagemann:  "Inaugural  Dissertation"  Erlangen,  1891;  Jagerroos:  "Archiv 
fur  Gynakologie,"  1902.   lxvii,  517. 

2  Murlin:    "American  Journal  of  Physiology,"  1910,  xxvii,  177. 


FOOD    REQUIREMENT   DURING    THE    PERIOD    OF    GROWTH       387 

This  shows  the  large  loss  of  maternal  protein  commencing 
immediately  after  conception  and  continuing  for  six  weeks. 
Only  during  the  last  two  weeks  is  there  a  marked  conservation 
of  protein  as  manifested  in  the  pronounced  nitrogen  retention. 

Some  very  instructive  experiments  have  been  performed 
to  ascertain  the  course  of  the  protein  metabolism  before  and 
after  pregnancy  in  women. 

Zacharjewski1  investigated  the  nitrogen  metabolism  of  9 
pregnant  women.  In  3  primiparae,  nourished  on  diets  con- 
taining an  average  of  16.5  grams  of  nitrogen,  there  was  an 
average  daily  retention  of  1.4  grams  in  the  mother's  organism 
for  thirteen  days  before  parturition.  In  6  multiparas  the  diet 
contained  20.6  grams  of  nitrogen,  and  there  was  a  daily  reten- 
tion of  5.12  grams  of  nitrogen  during  the  last  eighteen  days  of 
pregnancy.  The  figures  correspond  to  a  considerable  con- 
struction of  protein  tissue  within  the  organism.  After  child- 
birth there  was  always  a  loss  of  tissue  nitrogen  by  the  mother. 
In  1  case  nitrogen  equilibrium  was  established  on  the  fifth 
day,  and  in  another  on  the  fourth.  In  6  cases  the  loss  of  body 
nitrogen  continued  over  a  longer  time.  Zacharjewski  says 
that  the  process  of  involution  of  the  uterus  is  greatest  during 
the  first  five  to  seven  days  after  delivery,  and  the  high  nitrogen 
output  from  the  mother  is  the  result  of  this.  After  the  elimi- 
nation which  is  due  to  these  regressive  changes  there  is  a 
retention  of  nitrogen.  This  is  probably  attributable  to  the 
building  up  of  the  mammary  glands,  for  Slemons2  shows  that 
nitrogen  equilibrium,  once  established,  was  constantly  main- 
tained in  a  woman  who  did  not  nurse  her  child. 

The  complete  record  of  the  nitrogen  elimination  of  a  nurs- 
ing mother,  one  of  Slemons'  cases,  is  here  reproduced.  It  is 
especially  instructive  on  account  of  the  constancy  of  the 
quantity  of  nitrogen  in  the  diet.  The  woman  was  a  negress 
who  gave  birth  to  a  healthy,  vigorous  child. 

1  Zacharjewski:    "Zeitschrift  fur  Biologie,"  1894,  xxx,  405. 

2  Slemons:   "Johns  Hopkins  Hospital  Reports,''  1904,  xii,  121. 


388 


SCIENCE    OF   NUTRITION 


PROTEIN  METABOLISM   BEFORE  AND  AFTER  CHILDBIRTH 

(Weights  are  in  Grams) 


Days  Before  and 
After  Delivery. 


II 

IO 

9 

8 

7 

6 

5 

4 

3 

2 

I 

Delivery 
i 

2 

3 

4 

5 

6 

7 

8 

19 

20 

21 

22 

23 

24 

25 


N  IN 

Food. 


20.5 
19.2 
18.0 
16.9 

n-3 
19.2 
19.2 
19.2 
18.0 
14.9 

8.0 

4.2 

7-i 
13-7 
19.0 
19.0 
20.0 
20.0 
19.0 
11.0 

19.8 
18.8 
19.9 

17-3 
18.0 

18.7S 
19.0 


NlN 

Urine. 


Nin 
Feces. 


o-S3 


1. 14 


1.6 


Nin 
Milk. 


Nin 
Lochia. 


N 
Balance. 


+8.12 
+  2.07 

+6-57 
-0.77 

-2-95 
+  5-39 
+6-57 
+4-54 
+S-I2 
+  2.06 

—  4.00 

-9.66 
-2.79 
-o-S7 
-4-13 

+0.15 

-6.5 

-3-14 

-9.2 

+4.89 
+0.57 
+3-39 
+4-39 
+0.68 
+3-72 

—  0.16 


During  the  last  days  of  pregnancy  there  was  an  average 
daily  storage  of  2.98  grams  of  nitrogen,  and  for  eight  days  of 
the  puerperium  an  average  loss  of  4.5  grams.  Later,  between 
the  nineteenth  and  twenty-fifth  days  after  parturition ,  there  was 
an  average  daily  storage  of  2.52  grams  of  nitrogen.  This  may 
have  been  for  the  purpose  of  increasing  the  size  of  the  breasts. 
It  must  be  remembered  that  even  during  the  period  of  involu- 
tion an  increase  in  the  mammary  glands  may  have  been  taking 
place  at  the  expense  of  protein  derived  from  the  uterus.  So 
the  debit  balance  of  nitrogen  during  this  period  may  not  repre- 
sent all  the  protein  change  taking  place. 

An  elaborate  experiment  upon  the  subject  of  the  met- 


FOOD   REQUIREMENT   DURING   THE   PERIOD    OF   GROWTH       389 


abolism  of  the  pregnant  woman  was  carried  out  by  Hoffstrom,1 
and  extended  over  the  period  of  the  last  twenty-three  weeks 
of  pregnancy.  He  computes  the  probable  composition  of 
the  ovum  at  the  end  of  the  sixteenth  week  and  compares 
that  with  the  estimated  composition  of  the  child  at  birth,  and 
also  computes  the  constituents  of  the  food  retained  for  the 
growth  of  the  child  and  the  mother: 


Retained  from  Food  During 

Weeks. 

Twenty-three 

Composition 
of  Ovum, 

Total. 

For  Mother. 

For  Fetus. 

Sixteenth 
Week. 

N 

P 

Ca 

Mg 

Grams. 

310.05 

55-88 

34-31 

2-44 

Grams. 

208.57 

34-o 

4-2 

1.46 

Grams. 

101.48 
18.0 
30.12 
0.98 

Grams. 
4.28 
0.67 
O.38 
0.026 

There  was  an  irregular  retention  of  magnesium.  Rapid 
growth  of  the  fetus  began  during  the  twenty-ninth  week  of 
pregnancy,  at  which  time  the  calcium  retention  by  the  organ- 
ism greatly  increased  and  the  excretion  of  calcium  in  the 
feces  of  the  mother  diminished.  The  retention  of  materials 
by  the  mother  herself  represents  the  requirement  for  the 
growth  of  the  uterus,  the  breasts,  the  gluteal  and  leg  muscles. 

Hoffstrom  gives  the  following  computation  of  the  growth 
of  the  fetus: 


GROW 

TH  OF  THE  HUMAN  FETUS  COMPUTED  FROM  THE  TABLES 

OF  MICHEL 

Week 

N. 

P. 

Ca. 

Mg. 

Preg- 
nancy. 

Content 
of  Ovum. 

Added 
per  Week. 

Content 
of  Ovum. 

Added 
per  Week. 

Content 
of  Ovum. 

Added 
per  Week. 

Content 
of  Ovum. 

Added 
per  Week. 

16... . 

4.28 

I-I3 

O.67 

O.20 

O.38 

0.41 

O.026 

0.017 

20. . . . 

8.81 

I.47 

2.03 

O.095 

21  .  .  . 
28.... 

29 

40 ... . 

23.28 
105.76 

1. 81 

6.87 
6.87 

3-58 
18^93 

O.25 
i!a8 

1.28 

5-39 

30.51 

o.43 

2.09 
2.09 

O.234 
I.004 

0.017 

O.064 
O.064 

1  Hoffstrom:    "Skan.  Archiv  fur  Physiologie,"  1910,  xxiii,  326. 


390  SCIENCE    OF   NUTRITION 

It  is  obvious  that  during  the  last  ten  weeks  of  pregnancy 
a  diet  which  is  rich  in  calcium  is  indicated,  or  there  may  be  a 
withdrawal  of  calcium  from  the  mother's  bones.  Cows' 
milk  contains  much  calcium  and  is  a  highly  desirable  ad- 
dition  to   the    dietary   of    the    pregnant  woman.      (See   p. 

374-) 

Rubner  and  Langstein1  have  investigated  the  metabolism 
of  two  prematurely  born  infants.  One  of  them  was  born  at 
the  end  of  the  seventh  month  of  pregnancy  and  weighed 
2050  grams.  On  the  eighth  day  the  child  weighed  1900  grams, 
and  then  gained  an  average  of  28  grams  daily  until  the 
twenty-seventh  day,  when  it  weighed  2360  grams.  At  this 
point  respiration  experiments  were  introduced.  During  the 
next  eleven  days  the  child  gained  39  grams  daily.  During  this 
same  period  the  child  received  each  day  1.04  grams  of  nitrogen 
in  milk  and  retained  0.52  gram,  or  50  per  cent,  of  the  intake. 
At  this  period,  which  would  have  corresponded  to  the  begin- 
ning of  the  eighth  month  of  pregnancy,  the  addition  of  pro- 
tein to  the  child  amounted  to  only  one-half  that  computed 
by  Hoffstrom  for  the  fetus  of  the  same  age.  The  fat  retained 
per  day  averaged  14.6  grams.  The  diet  contained  126  calories 
per  kilogram  of  body  weight,  of  which  73  were  used  for  heat 
production  (973  calories  per  square  meter  per  day)  and  53 
were  deposited  in  the  growing  infant.  In  all,  42  per  cent,  of 
the  calories  ingested  in  the  food  were  retained  for  growth,  a 
remarkably  large  amount.  The  so-called  "growth  impulse" 
must  have  been  very  great.  The  second  prematurely  born 
infant  showed  the  same  capacity  for  protein  retention  as  the 
first,  but  the  amount  of  fat  retained  was  much  less. 

The  mother,  previously  described  as  having  been  investi- 
gated by  Slemons,  had  plenty  of  milk,  and  the  baby  gained  an 
average  of  30  grams  a  day  during  the  first  forty  days  of  his 
life. 

Slemons  remarks  that  the  low  protein  metabolism,  as  indi- 
cated by  the  urinary  nitrogen  of  the  period  of  settled  lactation, 
1  Rubner  and  Langstein:  "x\rchiv  fur  Physiologie,"  191 5,  p.  39. 


FOOD   REQUIREMENT   DURING   THE   PERIOD   OF    GROWTH       39 1 

is  a  proof  that  there  can  be  no  important  production  of  milk 
fat  from  protein. 

In  the  above  experiment  it  will  be  noticed  that  the  nitrogen 
of  the  milk  is  small  in  quantity  as  compared  with  the  urinary 
nitrogen.  On  a  strictly  vegetarian  diet  the  relation  would 
change.  Thus  Voit1  found  48.8  grams  of  nitrogen  in  the  milk 
of  a  cow  and  93.7  grams  of  nitrogen  in  her  urine  for  the  same 
period. 

The  influence  of  nutrition  on  the  production  of  milk  has 
been  the  object  of  countless  investigations,  but  unfortunately 
most  of  these  experiments  have  been  conducted  for  commercial 
purposes  on  cows  and  goats.  These  animals,  with  their  funda- 
mental ration  consisting  of  hay,  do  not  allow  of  the  ingestion 
of  simple  foods.  On  the  other  hand,  the  milk  supply  of  even  a 
large  bitch  is  very  limited  in  quantity  and  is  with  difficulty 
obtained.  The  writer  is  not  aware  of  any  systematic  obser- 
vations on  the  composition  of  human  milk  as  influenced  by 
food,  although  such  researches  would  seem  of  great  impor- 
tance. 

Perhaps  the  most  valuable  research  which  can  today  be 
used  is  an  old  one  of  Voit2  upon  a  bitch  weighing  34  kilograms. 
It  confirmed  the  previous  work  of  Kemmerich  and  of  Ssubotin, 
and  has  since  been  verified  by  Grimmer.3  The  animal  was 
given  meat  alone,  meat  and  starch,  meat  and  fat,  starch  alone, 
fat  alone,  and  was  also  starved.  The  influence  upon  the  milk 
secretion  was  found  to  be  comparatively  small.  The  research 
is  a  model  of  completeness,  the  plan  of  which  could  well  be 
copied  in  an  experiment  on  a  human  being. 

A  part  of  the  results  are  given  on  page  392. 

1  Voit:   "Zeitschrift  fur  Eiologie,"  1869,  v,  122. 

2  Voit:   Ibid.,  137. 

3  Grimmer:   "Biochemische  Zeitschrift,"  1014,  lxviii,  311. 


392 


SCIENCE    OF   NUTRITION 


INFLUENCE  OF  DIET  ON  THE  COMPOSITION  OF  THE  MILK  OF 
A  DOG  WEIGHING  34  KILOGRAMS 


Food. 

Milk. 

Day. 

Meat, 
Grams. 

Other 
Food. 
Grams. 

N, 
Grams. 

Amount 
C.C. 

N, 
Grams. 

Fat, 
Grams. 

Sugar, 
Grams. 

Protein, 
Per 
Cent. 

Fat, 
Per 
Cent. 

Sugar, 
Per 
Cent. 

6.... 
7.... 
8.... 
9.... 

IO 

II.... 

12.  .  .  . 
13...  . 

14.... 
I6.... 
17.... 

1000 
1000 
1000 

Mixed 
diet 
500 
500 

Starv. 

Starv. 

2000 
2000 

300  starch 
200  fat 
200  fat 

400  starch 
300  fat 

500  starch 

34 
34 
34 

17 
17 

68 
68 

115 

144 
13s 

151 
138 
168 

140 
118 
137 
158 
161 

1.1 
1.4 
1.1 

1.4 
1.2 
1.6 
1-5 

1.0 
1.1 

1.6 
i-7 

8.8 
10.8 
u-3 

13-9 
"•3 
i6.S 
13-8 

12.2 
10. 1 
16. 1 
14-7 

3-1 
3-8 
2.9 

3-4 
3-8 
4.2 
3-9 
3-0 
4-3 
4.4 
4-7 

5-97 
6.86 

6.22 

6-37 
5-83 
6.06 
6.36 
5.62 
5.41 
6.68 
6.78 

7.70 
7-5° 
8.39 

9.22 
8.19 
9-83 

9.24 
10.32 

7-39 
10.17 

9. 11 

2.71 
2.67 

2-15 

2.24 
2.78 
2.52 
2.65 
2.58 
3-II 
2.82 
2.91 

The  largest  quantity  of  milk,  as  well  as  the  richest  in  pro- 
tein, was  obtained  when  meat  or  meat  and  fat  were  ingested. 
Curiously  enough,  a  diet  of  500  grams  of  meat  and  300  grams 
of  fat  gave  milk  of  the  same  amount  and  quality  as  did  2000 
grams  of  meat.  It  is  usually  said  that  a  large  protein  diet 
stimulates  the  milk  secretion;  but  this  may  also  be  due  indi- 
rectly to  the  development  of  the  gland  cells. 

The  milk-sugar  content  was  scarcely  affected  by  the  diet, 
although  a  slight  percentage  increase  was  observed  after  starch 
ingestion. 

The  fat  content  was  increased  in  starvation  to  its  highest 
percentage.  It  was  not  very  greatly  affected  by  adding  fat  to 
a  meat  diet  and  it  was  greatly  reduced  by  giving  carbo- 
hydrates. 

The  action  of  fasting  on  the  fat  content  of  milk  is  better 
shown  in  the  herbivorous  goat.  The  writer1  gave  a  milch  goat 
a  constant  diet  of  hay,  cornmeal,  and  bran,  starved  the  animal 
for  two  days,  and  then  continued  the  former  diet.  The  fat 
content  of  the  milk  was  determined.  The  results  were  as 
follows: 

1  Lusk:   "Zeitschrift  fur  Biologie,"  1901,  xlii,  42. 


FOOD   REQUIREMENT   DURING   THE   PERIOD    OF   GROWTH       393 

Mh.k  in  C.C.  Fat  in  G.        Fat  in  Per  Cent. 

460 26.50  5.76 

470 25.90  5-52 

&■  ■■■■  23.90  6-23)Starvation. 

198 18.35  9-27/ 

232 18.75  8.08 

298 16.30  5.47 

348 14-04  5-6i 

362 22.30  6.16 

490 27.70  5.66 

In  fasting,  therefore,  the  fat  content  in  the  milk  of  the  her- 
bivorous goat  approaches  that  contained  in  the  carnivorous 
dog.  With  a  return  to  the  normal  diet  the  fat  content  in  goat's 
milk  is  reduced  to  its  former  level. 

Morgen,  Beger,  and  Fingerling1  find  that  a  diet  rich  in 
carbohydrate  and  poor  in  fat  produces  in  sheep  and  goats  a 
poor  milk  containing  little  fat,  although  the  general  condition 
of  the  animals  remains  perfect.  Addition  of  protein  increases 
the  quantity  of  the  milk  without  changing  the  low  fat  per- 
centage. Replacement  of  some  of  the  carbohydrate  with 
isodynamic  quantities  of  fat,  up  to  0.5  to  1.0  gram  per  kilo- 
gram of  animal,  largely  increases  the  fat  content  of  the  milk 
and  thereby  its  nutritive  value. 

Contrary  to  this  is  Jordan's-  statement  that  the  amount 
of  fat  in  the  fodder  is  without  influence  upon  the  fat  content 
of  a  cow's  milk.  Here  the  breed  of  the  cow  and  not  the  diet 
is  the  determining  factor.  The  German  agricultural  stations 
have  recently  reached  the  same  conclusion.  Morgen3  states 
that  the  principal  cause  of  the  difference  in  the  results  of  the 
experiments  on  cows  and  on  sheep  and  goats  lies  in  the  fact 
that  the  smaller  animals  produce  more  milk  for  their  weight 
than  do  cows,  and,  therefore,  the  milk  production  is  much 
more  dependent  on  the  food  supply. 

Newer  work  by  Prausnitz4  concludes  that  although  food 

1  Morgen,  Beger,  and  Fingerling:  "Landwirtschaft.  Versuchsstationen," 
1904,  lxi,  1. 

2  Jordan  and  Jenter:  "New  York  Agricultural  Experiment  Station,"  1897, 
Bulletin  132;  iyci,  Bulletin  197. 

3  Morgen,  Beger,  Fingerling,  and  Westhauser:  "Landwirtschaft.  Versuchs- 
stationen," 1908,  lxix,  295. 

4  Helle,  Miiller,  Prausnitz,  and  Poda:  "Zeitschrift  fur  Biologie,"  1912, 
Iviii,  355- 


394  SCIENCE   OF   NUTRITION 

does  not  determine  the  quantity  of  protein,  lactose,  or  ash  in 
cows'  milk,  yet  the  percentage  of  fat,  and  hence  the  caloric 
value  of  the  liter  of  milk,  may  be  considerably  influenced  by 
variations  in  the  diet. 

It  has  long  been  known  that  ingested  fat  may  appear  in 
the  milk  of  an  animal.  Gogitidse1  has  shown  that  after  giving 
linseed  oil  to  sheep  their  milk  fat  may  contain  33  per  cent,  of 
linseed  oil.  He  also  finds2  that  the  fat  of  linseed  oil  passes 
readily  into  human  milk,  and  that  the  fat  of  hempseed,  while 
influencing  the  composition  of  the  milk,  greatly  depresses  lac- 
tation during  the  period  of  its  ingestion. 

Hart  and  Humphrey3  have  shown  that  the  protein  con- 
tent of  the  milk  varies  very  little  even  though  a  cow  may  be 
losing  her  own  flesh  to  furnish  the  milk.  Thus,  when  a  cow 
was  given  a  food  with  a  "nutritive  ratio"  of  1:8,  that  is, 
1  part  of  protein  to  8  parts  of  carbohydrate  and  fat,  a  positive 
nitrogen  balance  was  present  provided  milk  protein  was  given 
in  the  diet,  but  when  protein  was  administered  in  the  bio- 
logically lower  form  of  wheat  protein,  a  negative  nitrogen 
balance  resulted.  The  quantity  of  protein  in  the  milk,  how- 
ever, remained  unchanged. 

These  facts  are  shown  in  the  following  table: 

N  Intake        Fecal        Absorbed        Urine  Milk         Balance 

per  Week,  N,  N,  N,  N,  N, 

Grams.         Grams.         Grams.         Grams.         Grams.         Grams. 

Wheat  ration 953  404  549  464  227  —  U2 

Milk  ration 968  350  618  286  220  +112 

"Milking  the  flesh  off  the  back"  is,  therefore,  a  reality. 
During  lactation  a  ration  high  in  protein  is  wisely  dictated 
and  the  biologic  status  of  the  protein  must  also  be  con- 
sidered. 

According  to  similar  laws,  Fingerling4  finds  that  a  fodder 
deficient  in  calcium  has  no  effect  upon  the  calcium  content 

1  Gogitidse:   "Zeitschrift  fur  Biologie,"  1904,  xlv,  365. 

2  Gogitidse:   Ibid.,  1905,  xlvi,  403  . 

3  Hart  and  Humphrey:   "Journal  of  Biological  Chemistry,"  1915,  xxi,  239. 

4  Fingerling:   "Landwirtschaft.  Versuchsstationen,"  1911,  lxxvi,  1. 


POOD    REQUIREMENT   DURING    THE    PERIOD    OF    GROWTH       395 

of  the  milk,  the  organism  providing  this  material.  Further- 
more, Lauder  and  Fagan1  found  that  the  addition  of  225  grams 
of  calcium  phosphate  to  a  fodder  already  containing  the  same 
content  of  that  salt  did  not  alter  the  calcium  content  of 
cows'  milk.  Von  Wendt2  states  that  ingestion  with  the  fodder 
of  sodium  chlorid,  calcium  carbonate,  calcium  hydrogen  phos- 
phate, calcium  glycerophosphate,  sodium  phosphate,  or  mag- 
nesium bromid  is  without  definite  influence  upon  the  com- 
position of  the  milk.  The  lactic  glands,  therefore,  prepare 
a  fluid  of  very  definite  composition  specifically  designed  for 
the  offspring  of  the  species. 

How  may  the  various  effects  of  diet  be  explained?  The 
subject  requires  a  knowledge  of  the  processes  going  on  in  the 
mammary  gland,  and  these  are  not  certainly  known.  It  has 
been  generally  believed  that  the  cells  of  the  mammary  glands 
undergo  a  fatty  metamorphosis  and,  themselves  breaking  up, 
pass  into  the  milk  (Voit,  Heidenhain).  The  milk  under  these 
circumstances  might  be  regarded  as  the  substance  of  an  organ, 
made  fluid. 

Schafer,3  however,  believes  the  process  to  be  one  of  secre- 
tion similar  to  that  in  the  salivary  glands,  where  the  cells  pre- 
pare the  special  constituents  and  pass  them  on  to  the  lumen. 
Thus  casein,  like  ptyalin,  may  be  specially  elaborated  within 
gland  cells. 

If  this  be  the  true  explanation,  the  influence  of  food,  in  the 
writer's  opinion,  may  be  readily  explained.  An  increased  pro- 
tein ingestion  furnishes  the  digestive  products  of  this  sub- 
stance in  liberal  quantities  and  may  increase  the  activity  of 
the  gland. 

The  milk-sugar  content  of  the  milk  remains  remarkably 
constant.  Cremer,4  for  example,  has  shown  that  the  per- 
centage of  milk-sugar  in  the  milk  is  unchanged  in  the  cow 

Lauder  and  Fagan:  "Proceedings  of  the  Royal  Society  of  Edinburgh," 
1914-15,  xxxv,  195. 

2  von  Wendt:   "Skan.  Archiv  fur  Physiologie,"  1909,  xxi,  89. 

3  Schafer:    "Text-book  of  Physiology,"  1898,  i,  667. 

4  Cremer:   "Zeitschrift  fur  Biologie,"  1899,  xxxvii,  78. 


396  SCIENCE   OF   NUTRITION 

after  diminishing  the  sugar  content  of  the  animal  by  inducing 
phlorhizin  diabetes. 

To  explain  the  fat  content  of  the  milk  the  writer  offers  the 
following  theory:  When  for  any  reason  sufficient  sugar  is 
not  oxidized  in  the  body  cells,  these  sugar-hungry  cells  attract 
fat.  It  has  already  been  seen  that  the  glycogen  and  fat  con- 
tent of  the  liver  are  antagonistic.  Before  lactation  sets  in,  the 
cells  of  the  mammary  glands  oxidize  sugar  and  there  is  no 
great  attraction  for  fat.  It  is  believed  that  milk-sugar  cannot 
be  formed  in  any  great  quantity  before  parturition,  because  it 
occurs  in  the  urine  only  postpartum}  That  milk-sugar  is 
not  formed  outside  of  the  mammary  glands  was  demon- 
strated by  Moore  and  Parker,2  who  completely  removed  these 
glands  from  a  goat  during  the  period  of  gestation,  and  later 
at  the  time  of  parturition  found  no  sugar  in  the  urine.  Had 
milk-sugar,  which  cannot  be  oxidized  by  the  organism,  been 
formed  outside  the  glands  it  would  have  accumulated  in  the 
blood  and  have  been  eliminated  in  the  urine.  When  in  the 
process  of  lactation  the  glucose  furnished  by  the  blood  is 
converted  into  milk-sugar  (which  cannot  be  burned  within 
the  organism),  the  mammary  cell  becomes  a  sugar-hungry 
cell  which  at  once  attracts  fat  from  the  blood.  This  theory 
of  the  writer  explains  the  production  of  milk  fat  by  the  process 
of  infiltration.  The  variation  of  the  percentage  of  fat  in  the 
milk  may  be  explained  by  the  quantity  of  fat  in  the  blood. 
During  starvation  the  blood  becomes  rich  in  fat  on  account  of 
the  transportation  of  tissue  fat  to  the  cells.  Administration  of 
sugar  at  once  reduces  the  supply  of  fat  in  the  blood.  But  if  fat 
be  ingested  with  carbohydrates  the  blood  becomes  rich  with 
this  fat  and  affords  material  for  a  rich  milk. 

Administration  of  good  cream  with  a  substantial  mixed 
diet  is  highly  to  be  recommended  for  nursing  mothers.  The 
daily  production  of  a  liter  of  milk,  which  has  a  value  of  640 
calories,  indicates  the  necessity  of  no  small  addition  to  the 

1Lemaire:   "Zeitschrift  fur  physiologische  Chemie,"  1896,  xxi,  442. 

2  Moore  and  Parker:    "American  Journal  of  Physiology,"  1900,  iv,  239. 


POOD   REQUIREMENT   DURING   THE   PERIOD   OF   GROWTH       397 

daily  ration,  if  the  woman  is  to  bear  satisfactorily  the  strain 
of  lactation.  Probably  this  extra  nourishment  is  best  given 
in  the  form  of  fat. 

Should  the  fat  of  the  milk  disagree  with  the  infant,  the 
trouble  may  be  due  to  the  kind  of  fat  ingested  by  the  mother. 
If,  however,  the  indigestion  be  due  to  a  large  percentage  of  fat, 
a  carbohydrate  diet  may  be  used  to  reduce  the  percentage  in 
the  milk. 

It  may  be  added  that  Voltz  and  Paechtner1  report  that 
after  moderate  ingestion  of  alcohol  only  minimal  quantities 
of  it  are  found  in  human  milk. 

A  very  important  fact  regarding  the  nutrition  of  the  young 
is  that  the  milk  of  one  race  is  specifically  adapted  to  the  growth 
of  the  offspring  of  that  particular  race.  Bunge2  found  that 
dogs'  milk  had  an  ash  of  exactly  the  same  composition  as  the 
ash  of  the  newborn  puppy.  The  ash  of  the  milk  was,  there- 
fore, perfectly  adapted  for  the  construction  of  new  puppy 
tissue.  It  was,  however,  very  different  in  composition  from 
human,  or  cows',  or  other  milk.  Only  in  the  case  of  iron  is 
the  quantity  lower  than  corresponds  to  the  composition  of 
the  offspring,  but  this  factor  is  offset  by  the  fact  that  the 
animal  when  newborn  is  richer  in  iron  than  it  is  at  any  other 
period  of  life.  Not  only  this,  but  the  caseins  of  different  milks 
are  different  in  chemical  behavior.  And  besides  this,  the 
rennin  of  the  stomach  is  said  to  be  specifically  adapted  for 
the  coagulation  of  the  casein  produced  by  the  female  of  the 
same  race.3 

Furthermore,  the  percentage  quantity  of  the  constituents 
in  the  milk  is  dependent  upon  the  rapidity  of  the  growth  of 
the  organism.  Bunge4  has  shown  this  in  the  following  com- 
parative table: 

1  Voltz  and  Paechtner:    "Biochemische  Zeitschrift,"  1913,  lii,  73. 

2  Bunge:   "Zeitschrift  fur  Biologie,"  1874,  x,  326. 

3  Kiesel:   "Pfliiger's  Archiv,"  1905,  cviii,  343. 

4  Bunge:   "Lehrbuch  der  physiologischen  Chemie,"  1898,  p.  118. 


398  SCIENCE    OF   NUTRITION 

Time  in  Days 
for  the  New- 
born Animal 

to  Double  100  Parts  of  Milk  Contain 

Its  Weight.  Protein.  Ash.  Calcium  Oxm. 

Man 180  1.6  0.2  0.328 

Horse 60  2.0  0.4  0.124 

Calf 47  3-5  o-7  0.160 

Kid 19  4-3  °-8  °-2I° 

Pig 18  5.9 

Lamb 10  6.5  0.9  0.272 

Dog 8  7.1  1.3  0.453 

Cat 7  9-5 

Camerer1  finds  that  human  milk,  drawn  three  to  twelve 
days  after  parturition,  contains  0.2  milligram  of  iron  (Fe203) 
per  100  c.c,  while  the  later  milk  contains  0.1  milligram.  The 
quantity  is  decreased  if  the  environment  or  the  condition  of 
the  mother  be  poor.2  Edelstein  and  Csonka3  state  that  1  liter 
of  cows'  milk  contains  0.7  milligram  of  Fe203  (0.6  to  1  mg.), 
which  is  one-third  to  one-half  the  quantity  contained  in 
human  milk.  Using  the  customary  methods  of  infant  feeding 
with  cows'  milk,  the  infant  obtains  too  little  iron. 

Blauberg4  reports  the  following  percentage  absorption  of 
the  ash  of  cows'  and  human  milk: 

Per  Cent.  Milk 
Kind  of  Milk.  Subject.  Ash  Absorbed. 

Cows' Infant.  60.70 

Diluted  cows' "  53-72 

Human "  79-42 

Human "  81.82 

Cows' Adult.  53-20 

The  quantity  of  calcium  in  cows'  milk  is  in  excess  of  the 
needs  of  the  human  infant. 

The  absorption  of  the  energy-containing  constituents  of 
the  milk  is  remarkably  constant.  This  is  illustrated  in  the 
following  table  made  from  Rubner's  experiments,5  which 
shows  the  physiologic  utilization  of  the  total  calories  of  milk: 

1  Camerer:   "Zeitschrift  fur  Biologie,"  1905,  xlvi,  371. 
2Jolles  and  Friedjung:     "Arch,  fiir  experimentelle  Path,  und  Pharm.," 
1901,  xlvi,  247. 

3  Edelstein  and  Csonka:  "Biochemische  Zeitschrift,"  1911-12,  xxxviii,  14. 

4  Blauberg:    "Zeitschrift  fiir  Biologie,"  1900,  xl,  44. 

B  Rubner:  Ibid.,  1899,  xxxviii,  380.  For  further  statistics  of  absorp- 
tion consult  Tangl:    "Pfliiger's  Archiv,"  1904,  civ,  453. 


FOOD    REQUIREMENT   DURING    THE    PERIOD    OF    GROWTH       399 

Per  Cent,  of  Calories 
Absorbed. 

Human  milk 91.6  to  94.0 

Diluted  cows'  milk 90.7 

Diluted  cows'  milk  +  milk-sugar 92.2 

Same  given  to  stunted  infant 87.1 

Cows'  milk  given  to  an  adult 89.8 

As  regards  the  relative  composition  of  average  cows'  and 
human  milk  five  and  one-half  months  after  parturition,  the 
following  comparison  may  be  made: 

PERCENTAGE   COMPOSITION  OF   COWS'  AND   HUMAN  MILK 

Cows'.  Human. 

I.>  II.*  1.3  II." 

Protein 3.41  3.2  1.0  1.52 

Fat 3.65  3.9  3.0  3.28 

Milk-sugar 4.81  5.1  6.4  6.50 

Or,  expressed  in  the  relative  calorific  value  of  the  different 
constituents,  this  comparison  may  be  given:5 

PERCENTAGE    DISTRIBUTION    OF    CALORIES    IN    COWS'    AND 

HUMAN  MILK 

Cows'.  Human. 

I.  I. 

Protein 21.3  7.4 

Fat 49.8  43.9 

Milk-sugar 28.9  48.7 

Here,  then,  there  are  tremendous  differences  of  composi- 
tion, which  fact  forces  the  conclusion  that  cows'  milk  is  not  to 
be  substituted  for  human  milk  in  rearing  a  child. 

Patein  and  Daval6  find  that  human  milk  after  the  first 
month  of  lactation  contains  but  0.8  to  1  per  cent,  of  casein. 

Another  distinction  between  cows'  and  human  milk  is  that 
the  former  contains  but  little  extractive  nitrogen,  while  the 
latter  may  contain  18  to  20  per  cent.7  in  that  form.  These 
nitrogenous   extractives   contain   a   considerable   amount   of 

1  Rubner:   Von  Leyden's  "Handbuch,"  1903,  i,  95. 

2  Van  Slyke,  "Modern  Methods  of  Testing  Milk  and  Milk  Products,"  1907. 
Average  of  5552  American  analyses. 

3  Rubner  and  Heubner:  "Zeitschrift  fur  ex.  Pathologie  und  Therapie," 
1905,  i.  1. 

4  Soldner:  "Zeitschrift  fur  Biologie,"  1896,  xxxiii,  66.  Average  of  the 
milk  of  5  women. 

6  Rubner:    "Energiegesetze,"  1902,  p.  418. 

6  Patein  and  Daval:   "Journal  de  Pharm.  et  de  Chimie,"  1905,  xxii,  193. 

7  Rubner  and  Heubner:   Loc.  cit. 


400  SCIENCE   OF   NUTRITION 

carbon.  Meigs  and  Marsh1  state  that  human  milk  contains 
i  per  cent,  of  unknown  extractive  substances  which  are  al- 
most free  from  nitrogen.  This  is  probably  one  of  the  causes 
of  the  increase  of  the  ^  ratio  (see  p.  38)  to  over  unity  in  the 
urine  of  breast-fed  infants. 

From  the  standpoint  of  chemical  analysis  Abderhalden2 
could  find  no  distinctive  quantitative  difference  between  the 
amounts  of  various  amino-acids  in  human  and  bovine  milks. 

A  recent  analysis3  presents  the  following  data  as  regards 
the  probable  composition  of  human  milk: 

Per  Cent. 

Fat 3.30 

Lactose 6.50 

Proteins  combined  with  calcium 1.50 

Calcium  chlorid 0059 

Monopotassium  phosphate 0.069 

Sodium  citrate 0.055 

Potassium  citrate o.  103 

Monomagnesium  phosphate 0.027 

The  large  protein  content  of  cows'  milk  may  be  bad  for  the 
child.  In  the  first  place  it  clots  in  a  heavy  mass  in  the  baby's 
stomach;  and  in  the  second  place,  even  though  it  be  digested,  it 
is  relatively  much  above  the  requirement  of  the  organism,  and 
its  specific  dynamic  action  increases  the  amount  of  heat  pro- 
duced.    (See  p.  406.) 

If  cows'  milk  be  diluted  with  2  or  more  parts  of  water 
its  protein  content  may  approach  that  of  human  milk  and  its 
precipitation  by  rennin  in  the  stomach  is  in  the  form  of  flakes. 
The  writer's  father,4  following  a  suggestion  of  Abraham  Jacobi, 
used  oatmeal  or  barley  water  as  a  diluent  of  milk  given  to 
babies.  The  precipitation  of  cows'  casein  takes  place  in  very 
fine  flakes  when  the  milk  is  mixed  with  barley  water,  as  was 
shown  by  Chapin. 

Chapin's  observations,  in  which  the  writer  assisted,,  have 
been  confirmed  by  White,5  who  says  that  this  action  is  due  to 
the  presence  of  f  to  1  per  cent,  of  dissolved  starch. 

1  Meigs  and  Marsh:  "Journal  of  Biological  Chemistry,"  1913-14,  xvi,  147. 

2  Abderhalden  and  Langstein:  "Zeitschrift  fur  physiologische  Chemie," 
1910,  lxvi,  8. 

3  Bosworth:   "Journal  of  Biological  Chemistry,"  1915,  xx,  707. 

4  Lusk,  W.  T.:  "Science  and  Art  of  Midwifery,"  1891,  p.  258. 

6  White:  "Journal  of  the  Boston  Society  of  Medical  Sciences,"  1900,  v,  130. 


FOOD   REQUIREMENT   DURING   THE   PERIOD    OF   GROWTH       401 

The  dilution  of  cows'  milk,  however,  reduces  the  quantity 
of  fat  and  carbohydrates,  and  these  must  therefore  be  added  to 
the  milk  in  order  to  make  a  proper  diet  for  a  child. 

To  obtain  a  sufficient  fat  content,  "top  milk,"  rich  in  fat, 
may  be  taken  from  milk  which  has  been  standing,  and  may  be^ 
mixed  with  water.     Milk-sugar  may  then  be  added. 

Such  a  milk,  called  "modified  milk,"  was  first  introduced 
by  Rotch,  of  Boston.  Infants  are  brought  up  on  it  with  greater 
success  than  was  the  case  when  undiluted  cows'  milk  was  given. 

Human  milk  has  a  varying  calorific  value  dependent 
largely  on  the  amount  of  fat  present.  Thus  Schlossmann1 
finds  that  the  calorific  value  per  liter  of  nineteen  samples  of 
milk  from  19  women  averages  719  calories,  with  a  maxi- 
mum of  876  and  a  minimum  of  567.  The  milks  having  the 
largest  fuel  value  contained  5.2  to  5.1  per  cent,  of  fat,  while 
that  having  the  lowest  contained  only  1.8  per  cent. 

The  amount  of  the  child's  metabolism  is  dependent  on 
his  size.  Rubner  states  that  a  baby  weighing  4  kilograms 
produces  422  calories,  an  adult  weighing  40  kilograms,  2106 
calories,  but  that  the  metabolism  per  unit  of  area  is  the  same. 

Rubner  and  Heubner2  summarize  their  results  on  the 
metabolism  of  differently  conditioned  children  as  follows: 

Calories  per  Sq. 
Weight  in  Kg.       Meter  of  Surface. 

Infant  of  stunted  growth 3  1090 

Infant  at  the  breast 5  1006 

Infant  on  cows'  milk 8  1143 

Infant  at  the  breast 10  1219 

The  metabolism  in  all  these  cases  was  essentially  the  same 
per  unit  of  area. 

In  the  last  case  the  very  noticeable  amount  of  muscle 
movement  and  crying  while  the  child  was  in  the  respiration 
apparatus  increased  the  metabolism.  Further  details  regard- 
ing this  case  give  a  very  complete  picture  of  the  metabolism  of 
an  infant.     The  child  weighed  4.06  kilograms  at  birth,  and 

1  Schlossmann:   "Zeitschrift  fur  physiologische  Chemie,"  1903,  xxxvii,  340. 

2  Rubner  and  Heubner:  "Zeitschrift  fiir  ex.  Pathologie  und  Therapie," 
1905,  i,  1. 

26 


402 


SCIENCE    OF   NUTRITION 


about  10  kilograms  at  the  time  of  the  experiment  when  five 
and  a  half  months  old.     He  was  given  his  mother's  milk. 

The  first  day  of  the  experiment  the  child  was  very  uncom- 
fortable on  account  of  his  new  environment.  The  last  day  he 
was  given  only  a  small  quantity  of  tea,  and  was  therefore  in 
a  state  of  practical  starvation.  The  carbon  dioxid  excretion 
on  these  days  was  as  follows: 

Grams  of  CO2 
in  24  Hours. 


First 278.8 

Second 21Q.9 

Third 228.1 

Fourth 231. 1 

Fifth 218.2 

The  diet  on  the  second,  third,  and  fourth  days  consisted  of 
1258  grams  of  human  milk  per  day  containing: 

Total  nitrogen 1.99  grams. 

Fat 37-73      " 

Milk-sugar 85.5        " 

Of  the  total  nitrogen  only  1.63  grams  were  contained  in 
true  protein,  the  rest  being  in  nitrogenous  extractives.  The 
percentage  composition  of  this  milk  is  given  on  page  399.  Its 
actual  nutritive  value  was  634.5  calories. 

The  balance  sheet  of  the  respiration  experiment  showed  the 
following  daily  result: 

METABOLISM   OF   AN*  INFANT 


Day. 

Food. 

Milk. 
None 

N  IN 

Food. 

N  IN 

Urine. 

NiN 

Total 
Excreta. 

N  Bal- 
ance. 

C  IN 

Food. 

C  in  Ex- 
creta. 

C  Bal- 
ance. 

2,3,4- 
5 

Grams. 
1.99 

Grams. 

1. 13 

1. 18 

Grams. 

i-53 
1. 18 

Grams. 
+  0.46 
-I.18 

Grams. 

63-7 
.... 

Grams. 
65.8 
60.8 

Grams. 

—  2.1 

-60.8 

The  infant  was  nearly  in  calorific  equilibrium  during  the 
period  of  milk  ingestion.  There  were  634.5  available  calories 
in  the  milk  and  660.5  calories  produced  in  the  metabolism. 

The  quantity  of  the  protein  metabolism  was  extremely 
small,  being  9.6  grams  according  to  the  usual  method  of  com- 
putation.    The  milk  contained  protein  to  the  extent  of  7  per 


FOOD   REQUIREMENT   DURING   THE   PERIOD    OF    GROWTH       403 

cent,  of  its  total  calorific  content.  Of  this  only  5  per  cent,  was 
metabolized  and  2  per  cent,  was  added  to  the  body.  The 
metabolism  of  an  infant  may  therefore  be  maintained  on  a  diet 
in  which  5  per  cent,  of  the  energy  is  supplied  by  protein  and 
95  per  cent,  by  fats  and  carbohydrates. 

The  specific  dynamic  action  of  the  milk  was  almost  negli- 
gible, the  metabolism  being  approximately  the  same  during  the 
period  of  feeding  as  during  that  of  starvation.  Curiously 
enough,  the  protein  metabolism  was  the  same  on  days  of  milk 
ingestion  as  in  starvation.  The  "wear  and  tear"  quota  was 
covered  by  a  "repair"  quota  of  equal  amount.     (See  p.  282.) 

This  child  gained  normally  in  weight  before  and  after  the 
respiration  experiment,  but  during  that  time  struggling  and 
crying  prevented  fat  addition  to  the  otherwise  well-developed 
normal  infant.1 

Schlossmann  and  Murschhauser2  note  that,  whereas  during 
the  first  and  second  days  of  fasting  an  infant  may  eliminate 
16  and  15  milligrams  of  urinary  nitrogen  per  kilogram  of  body 
weight,  return  to  a  normal  diet  results  in  the  elimination  of 
only  8  milligrams  per  kilogram.  This  illustrates  the  avidity 
with  which,  under  favorable  conditions,  all  available  protein 
is  used  for  growth. 

W.  Camerer,  Jr.,3  showed  that  a  breast-fed  infant  nine 
months  old  may  ingest  480  calories  in  the  milk,  produce  420 
calories  in  metabolism,  and  add  60  calories  to  his  body,  or  15 
per  cent,  of  the  energy  content  of  the  diet.  In  this  case  40  per 
cent,  of  the  protein  intake  was  added  to  the  growing  organism. 

Rubner  and  Heubner4  have  reported  a  respiration  experi- 
ment on  a  child  seven  and  a  half  months  old  nourished  with 
modified  cows'  milk.  The  intake  was  682.8  calories,  the 
metabolism  593.2,  leaving  89.6  calories,  or  12.2  per  cent,  for 
addition  to  the  child's  organism. 

It  is  remarkable  that  a  child's  intuitive  appetite  should 

1  Heubner:    "Jahrbuch  fiir  Kinderheilkunde,"  1905,  lxi,  430. 

2  Schlossmann  and  Murschhauser:  "Biochemische  Zeitschrift,"  1913,  lvi,  355. 

3  W.  Camerer,  Jr.:   "Zeitschrift  fiir  Biologie,"  1902,  xliii,  1. 

4  Rubner  and  Heubner:  Ibid.,  1899,  xxxviii,  345. 


404  SCIENCE   OF   NUTRITION 

determine  the  ingestion  of  nutriment  necessary  to  cover  the 
energy  requirement  of  his  organism,  and  a  small  addition  for 
normal  development.  A  reduction  of  15  per  cent,  in  the  in- 
take of  food  would  bring  his  prosperous  growth  to  a  standstill. 

Heubner1  says  that  the  average  normal  infant  requires  100 
calories  per  diem  per  kilogram  of  body  weight  for  normal  nutri- 
tion during  the  first  three  months  of  his  life,  90  calories  during 
the  second  three  months,  and  80  and  less  thereafter.  The 
energy  content  of  the  food  should  never  sink  below  70  calories 
per  kilogram,  which  is  about  the  maintenance  minimum. 

The  so-called  "scientific  feeding"  of  infants  is  unworthy  of 
the  name  unless  the  calorific  requirement  is  carefully  consid- 
ered. From  lack  of  this  knowledge  babies  are  frequently  sys- 
tematically starved. 

It  is  evident  from  this  discussion  that  the  fundamental, 
basal  metabolism  of  the  infant  cannot  be  determined  during 
long  periods  in  which  crying  is  an  ever-entering  factor.  Schloss- 
mann and  Murschhauser,2  for  example,  have  found  that  the 
metabolism  of  an  infant  may  double  during  an  hour  of  move- 
ment when  the  baby  would  not  be  quieted,  but  cried  intensely. 
The  resting  metabolism  of  this  child  five  months  old  was 
estimated  at  859  calories  per  square  meter  of  surface  in 
twenty-four  hours.  The  same  authors3  have  shown  that  a 
change  of  environmental  temperature  between  220  and  17°  C. 
has  no  influence  upon  the  heat  production  of  the  infant. 
Hasselbalch4  in  1904  investigated  the  metabolism  of  newborn 
babies  and  established  the  fact  that  the  respiratory  quotient 
of  the  child  at  birth  was  about  unity,  which  indicates  that  the 
earliest  source  of  its  energy  requirement  is  derived  from  stored 
glycogen.  This  was  confirmed  by  Bailey  and  Murlin,  who 
also  showed  that  on  account  of  insufficient  nourishment  the 

1  Heubner:    "Berliner  klinische  Wochenschrift,"  1901,  xxxviii,  449. 

2  Schlossmann  and  Murschhauser:  "Biochemische  Zeitschrift,"  1910,  xxvi, 
14. 

3  Schlossmann  and  Murschhauser:  Ibid.,  191 1,  xxxvii,  1. 

4  Published  in  Danish;  English  translation  by  F.  G.  Benedict  and  Talbot 
in  "The  Physiology  of  the  Newborn  Infant,"  1915,  Carnegie  Institution  Bul- 
letin 233. 


FOOD    REQUIREMENT   DURING    THE    PERIOD    OF    GROWTH       405 

respiratory  quotient  fell  to  the  fasting  level  within  twenty- 
four  hours. 

The  principal  recent  work  upon  this  subject  of  the  metab- 
olism of  children  has  been  accomplished  in  the  United  States. 
It  was  begun  by  John  Howland  and  continued  by  Benedict 
and  Talbot,  and  by  Murlin  and  Bailey,  and  Murlin  and 
Hoobler. 

Howland's1  experiments  are  the  only  reported  calori- 
metric  observations  upon  infants,  and  the  close  concordance 
between  direct  and  indirect  calorimetry  as  observed  in  hourly 
periods  in  these  experiments  gave  confidence  to  subsequent 
observers  that  by  the  careful  determination  of  the  respiratory 
metabolism  alone  the  actual  heat  production  could  be  readily 
computed. 

Howland  gives  the  following  summary  of  work  with  a 
normal  male  infant  (Child  I)  five  months  old  and  with  a  boy 
(Child  III)  six  months  old  who  weighed  only  3  kilograms  and 
was  literally  "skin  and  bones."  The  children  were  fed  with 
diluted  milk  with  the  addition  of  milk-sugar: 

CORRESPONDENCE   BETWEEN  DIRECT  AND  INDIRECT  CALOR- 
IMETRY IN   INFANTS 


Food. 


Child  I      Milk. 


Same  -f-  nutrose. 
Same  +  nutrose. 


Fasting. 


Child  III     Milk. 

Milk. 


Calories  per  Sq.  M. 

per 

Day. 

Direct. 

Indirect. 

1046 

1084 

1113 

1174 

1196 

1164 

1218 

1179 

1204 

1180 

1235 

1212 

1181 

I25O 

1 106 

1177 

1226 

II56 

1301 

1243 

858 

793 

913 

933 

825 

840 

Differ- 
ence i.v 
Per  Cent. 


3 
0.6 


1  Howland:      "Zeitschrift   fur   physiologische    Chemie,"    1911,    lxxiv,    1; 
Transactions  XV  International  Congress  of  Hygiene,  191 2,  ii,  Part  2,  438. 


406  SCIENCE   OF   NUTRITION 

To  compute  the  surface  area  of  children  Lissauer's  formula 
(10.3  ^Weight2)  is  usually  employed,  though  Howland  has 
suggested  one  of  still  greater  accuracy. 

Just  as  in  the  case  of  the  adult  (see  p.  476),  the  emaciated 
organism  of  an  infant  produces  less  heat  per  square  meter  of 
surface  than  the  normal  organism.  Howland  reported  an- 
other case  in  which  he  determined  the  heat  production  of  an 
eight-year  old  child,  emaciated  to  a  most  extreme  degree  and 
almost  devoid  of  musculature.  The  average  heat  production 
was  13.2  calories  per  hour,  or  809  per  square  meter  of  surface 
per  day. 

Lusk1  pointed  out  that,  whereas  the  metabolism  of  the  dog 
and  of  a  human  dwarf  was  about  775  calories  per  square  meter 
per  day  under  conditions  of  complete  rest,  that  of  the  two 
normal  infants  who  were  the  subjects  of  Howland's  experi- 
ments was  1 100  calories  per  unit  of  surface.  Howland's  work 
furthermore  showed  that  when  nutrose  was  added  to  the  diet 
there  was  a  pronounced  specific  dynamic  action,  the  heat 
production  rising  from  14.9  to  18.8  calories  per  hour,  an  in- 
crease of  26  per  cent.  Vigorous  crying  also  increased  the 
metabolism  in  the  same  child  from  14.85  to  20.6  calories  per 
hour,  an  increase  of  39  per  cent.     (See  p.  407.) 

In  1 9 14  Benedict  and  Talbot2  published  a  monograph 
which  included  metabolism  studies  upon  37  infants,  as  the 
result  of  which  they  concluded,  "We  find  ourselves  thoroughly 
convinced  that  the  metabolism  is  determined  not  by  the  body 
surface,  but  by  the  active  mass  of  protoplasmic  tissue." 

Bailey  and  Murlin3  published  observations  upon  the 
metabolism  of  6  newborn  infants  shortly  after  the  publication 
of  a  preliminary  communication  by  Benedict  and  Talbot4 
upon  the  same  subject,  which  they  later  reported  in  detail.5 

1Lusk:  "Transactions  XV  International  Congress  of  Hygiene,"  1912,  ii, 
Part  2,  400. 

2  Benedict  and  Talbot:  "The  Gaseous  Metabolism  of  Infants,"  Carnegie 
Institution  of  Washington,  1914,  Bulletin  201. 

3  Bailey  and  Murlin:    "American  Journal  of  Obstetrics,"  1915,  lxxi,  526. 

4  Benedict  and  Talbot:  "Amer.  Jour,  of  Diseases  of  Children,"  19 14,  viii,  1. 

5  Benedict  and  Talbot:  "The  Physiology  of  the  Newborn  Infant,"  Carnegie 
Institution  of  Washington,  1915,  Bulletin  233. 


FOOD   REQUIREMENT   DURING   THE    PERIOD    OF    GROWTH       407 

In  the  same  year  Murlin  and  Hoobler1  published  their  results 
concerning  the  energy  metabolism  of  10  hospital  children 
and  at  the  same  time  summarized  the  work  of  their  predeces- 
sors and  contemporaries.  They  pointed  out  that  the  heat 
production  of  sleeping  children  between  the  ages  of  two  months 
and  one  year  was  about  2.5  calories  per  kilogram  per  hour;  in 
other  words,  they  state  that  60  calories  per  kilogram  per  day 
may  be  called  the  heat  production  of  normal,  recently  fed, 
sleeping  infants.  The  newborn  babies  had  a  metabolism  less 
than  this,  which  did  not  exceed  48  calories  per  kilogram  per 
day.  Murlin  was  the  first  to  emphasize  that  when  age  was 
taken  into  consideration  there  was  a  constancy  in  the  heat 
production  per  square  meter  of  surface.  Two  charts  taken 
from  Murlin  illustrating  the  relations  described  are  repro- 
duced on  pages  408  and  409,  and  the  chart  of  Du  Bois  showing 
the  influence  of  age  on  metabolism  should  also  be  consulted. 
(See  p.  127.) 

In  gratifying  accord  with  this  interpretation  is  the  more 
recent  announcement  of  Benedict  and  Talbot  that  in  48  new- 
born infants  80  per  cent-  of  their  cases  showed  a  metabolism 
which  was  within  6  per  cent,  of  640  calories  per  square  meter 
per  day.  Per  kilogram  of  body  weight  48  calories  is  given  by 
them  as  the  maintenance  minimum. 

In  practical  dietetics  one  must  add  to  the  maintenance 
requirement  sufficient  nourishment  to  provide  for  the  crying 
of  the  child,  and  also  the  very  considerable  quota  to  meet  the 
demands  of  growth. 

The  amount  of  energy  expended  by  the  crying  of  an  infant 
will  vary  with  the  infant,  for  during  this  form  of  exercise  the 
heat  production  is  raised  at  least  40  per  cent.  It  is  certain 
that  Heubner's  figure  of  100  calories  per  kilogram  of  body 
weight  during  the  first  month  of  the  infant's  nutrition  is  in 
excess  of  the  requirement.  Probably  80  calories  per  kilogram 
of  body  weight  will  be  found  to  suffice  during  the  whole  of  the 

1  Murlin  and  Hoobler:  "Amer.  Jour,  of  Diseases  of  Children,"  1915, 
ix,  81. 


4o8 


SCIENCE   OF   NUTRITION 


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Fig.  24. — Showing  relation  of  heat  production  to  body  weight.  All  infants 
whose  metabolism  has  been  studied  by  von  Pettenkofer  or  Regnault-Reiset 
methods. 


FOOD   REQUIREMENT   DURING   THE   PERIOD    OF   GROWTH       409 


Fig.  25. — Showing  relation  of  heat  production  to  skin  surface.  All  infants 
whose  metabolism  has  been  studied  by  von  Pettenkofer  or  Regnault-Reiset 
methods. 


4IO  SCIENCE   OF   NUTRITION 

first  year  of  life,  and  the  physician  should  remember  very  defi- 
nitely the  lower  limits.  It  is  not  infrequent  that  a  crying 
infant  is  merely  hungry. 

Oppenheimer1  first  called  attention  to  the  fact  that  the 
growth  in  grams  of  normal  breast-fed  children  of  the  same  age 
may  be  nearly  proportional  to  the  quantity  of  milk  ingested. 
Here  the  milk  presumably  had  the  same  calorific  value  through- 
out the  experiment,  although  this  could  not  be  determined. 
The  quantity  of  milk  taken  at  each  meal  was  found  by  weigh- 
ing the  infant  before  and  after  nursing.  Oppenheimer's  table 
is  here  reproduced: 

GROWTH   IN   GRAMS   FOR    1   KG.   MILK 

Feer's         Oppenheimer's 
Month.  Subject.  Subject. 

1 33-8  95-Q 

II 191. 2  20I. I 

HI I20.3  I38.S 

IV 102.6  103.3 

V 57-7  120.8 

The  proportion  of  growth  to  milk  given  was  practically  the 
same  during  the  second,  third,  and  fourth  months  of  these 
children's  lives. 

That  the  growth  of  suckling  pigs  may  be  proportional  to 
the  calorific  value  of  the  milk  has  been  shown  by  work  ac- 
complished by  Dr.  L.  C.  Sanford  and  Dr.  Margaret  B.  Wilson2 
in  the  writer's  laboratory.  Newborn  pigs  of  two  litters 
were  reared  on  skimmed  cows'  milk  and  on  the  same  milk 
fortified  with  2  and  3  per  cent,  of  glucose  or  of  milk- 
sugar.  The  experiments  were  continued  from  fourteen  to 
sixteen  days.  The  results  obtained  in  these  experiments  are 
thus  tabulated: 

1  Oppenheimer:   "Zeitschrift  fur  Biologie,"  1901,  xlii,  147. 

2  Wilson:   "American  Journal  of  Physiology,"  1902,  viii,  197. 


FOOD    REQUIREMENT   DURING   THE    PERIOD    OF    GROWTH       411 
GROWTH   OF   SUCKLING   PIGS 


Wilson. 

Sanford  and  Lusk. 

Skimmed 
Milk. 

Lactose. 

Glucose. 

Skimmed 
Milk. 

Lactose. 

Glucose. 

Weight  in  grams  when 
born 

Weight  in  grams  when 
killed 

Growth  in  per  cent 

Milk  fed  in  c.c 

Available  calories  fed .  . 
Growth    in    grams    per 

liter  of  milk 

Growth    in    grams    per 

1000  calories  fed 

1,322 

2,205 

883 

66.8 

10,925 

4,053 

81 
218 

1,295 

2,435 

1,140 

88.0 

11,005 

5,216 

114 
215 

14S5 

2471 

986 

66.4 

9707 

4620 

101 
213 

1000 

1246 

264 

26.4 

6826 

2339 

38 

114 

1050 

1890 
838 

79-7 
8836 

3736 

95 

222 

"52 

2000 

848 

73-6 

948i 

3972 

89 

213 

It  is  seen  that  the  growth  of  the  pigs  in  grams  was  directly 
proportional  to  the  calorific  value  of  the  food  to  the  organism. 
The  one  exception  was  that  of  an  ill-nourished  pig  fed  with 
skimmed  milk.  This  was  an  improperly  nourished  animal 
taking  too  little  food  and  remaining  behind  his  fellows  in 
normal  development.  But  that  5  out  of  6  pigs  of  different 
litters,  of  different  sizes  and  differently  fed,  should  have  gained 
in  weight  respectively  213,  214,  215,  218,  and  222  grams  per 
thousand  calories  in  the  food  ingested  seems  more  than  a 
coincidence. 

It  may  be  further  calculated  that  to  form  1  kilogram  of 
body  substance  containing  28.7  grams  of  nitrogen  and  866 
calories  requires  the  ingestion  of  4637  calories  in  the  food. 

A  pig  doubles  in  weight  in  eighteen  days  after  birth.  The 
pig  of  Dr.  Wilson,  brought  up  on  skimmed  milk  with  3  per 
cent,  of  milk-sugar  added,  nearly  doubled  in  weight  in  sixteen 
days. 

Comparing  the  fuel  value  of  sows'  milk  and  that  of  the 
skimmed  cows'  milk  to  which  milk-sugar  had  been  added, 
the  following  results  are  significant.  Of  100  calories  in  the 
food  there  are: 


412  SCIENCE   OF   NUTRITION 

Skimmed  Milk  +  3  Per 
Sows'  Milk.1  Cent.  Milk-sugar. 

Protein 19.5  36.5 

Fats 72.0  2.5 

Carbohydrates 8.5  61.0 

It  is  apparent  from  this  that  normal  growth  of  the  young 
organism  may  be  attained  by  the  replacement  of  fat  by  milk- 
sugar  in  isodynamic  quantity.  This  fact  may  become  of 
importance  in  infant  feeding. 

Dr.  Wilson  found,  when  the  pigs  reared  on  these  diets 
were  killed  and  their  composition  compared  with  that  of  3 
pigs  of  the  same  litter  which  were  killed  at  birth,  that  there  was 
a  retention  for  growth  of  18  to  19  per  cent,  of  the  energy  in  the 
food. 

In  children  Camerer  found  15  per  cent.,  Rubner  and  Heub- 
ner  12.2  per  cent,  so  retained. 

The  percentage  of  calcium  (CaO)  in  the  dry  solids  of  the 
pigs  reared  on  the  various  skimmed  milks  was  8.29,  8.02,  and 
8.13,  showing  that  the  absorption  of  calcium  depended  on  the 
growth  of  the  organism,  and  not  on  a  variation  in  the  quan- 
tity ingested. 

There  is  apparently  a  fixed  and  definite  tendency  toward 
uniform  growth.  Schapiro2  found  that  if  young  kittens  were 
chloroformed  twice  daily  their  growth  was  retarded  in  compari- 
son with  normal  control  animals.  However,  on  stoppage  of 
the  chloroform  treatment,  the  greater  rapidity  of  growth  dur- 
ing an  after  period  fully  compensated  for  the  earlier  delay  in 
development.     (See  Chapter  XIII,  p.  375.) 

Lusk  has  shown  that  if  an  amino-acid,  such  as  alanin,  be 
added  to  the  diet  of  a  dog  there  is  a  considerable  stimulation 
of  metabolism.  (See  p.  240.)  Mendel,  in  unpublished  experi- 
ments (cited  here  by  permission),  has  demonstrated  that  the 
addition  of  alanin  to  the  diet  of  growing  rats  has  no  influ- 
ence whatever  upon  their  rate  of  growth.     Rubner3  set  forth 

1  Calculated  from  Ostertag  and  Zuntz:  "Landwirtsch.  Jahrbiicher,"  1908, 
xxxvii,  2ii. 

2  Schapiro:  Proceedings  of  the  Physiological  Society,  "Journal  of  Physiol- 
ogy," 1905-6,  xxxiii,  p.  xxxi. 

3  Rubner:  "Archiv  fur  Hygiene,"  1908,  Ixvi,  43. 


FOOD   REQUIREMENT   DURING   THE   PERIOD    OF    GROWTH       413 

that  the  conditions  which  determine  the  "wear  and  tear" 
quota  of  protein  metabolism  and  those  which  determine  growth 
by  the  addition  of  a  "growth  quota"  from  protein  in  the  diet, 
are  entirely  dissimilar,  although  without  metabolism  growth 
is  impossible.  Mendel's  experiments  show  conclusively  that 
the  stimulation  of  the  general  metabolism  itself  in  no  way 
affects  the  fundamental  capacity  to  grow. 

Another  instance  which  demonstrates  that  the  young 
organism  may  grow  in  proportion  to  the  energy  ingested  in  the 
food  is  brought  to  light  by  calculations  based  on  the  work  of 
E.  Rost.1  This  author  gave  meat,  fat,  and  bone-ash  to  three 
dogs  of  the  same  litter,  the  experiment  starting  on  the  ninety- 
eighth  day  of  their  lives  and  continuing  eighty-eight  days. 
The  writer  has  thus  calculated  the  results : 

Dog  I.  Dog  II.  Dog  III. 

Weight  in  grams  at  start 3,200  2,200  4,150 

Weight  in  grams  at  end 6,280  4,640  8,750 

Growth  in  grams 3.080  2,440  4,600 

Growth  in  per  cent 96  no  no 

Available  calories  ingested 24,420  17,336  34,276 

Gain    in    grams    per    100    calories 

ingested 122  141  134 

It  is  worthy  of  note  that  these  growing  dogs,  fed  with  meat 
and  fat,  gained  in  weight  nearly  the  same  number  of  grams 
per  1000  calories  ingested  in  the  food.  This  law  of  growth 
seems  reasonably  established.  It  simply  expresses  the  fact 
that  during  the  normal  development  of  the  young  of  the  same 
age  and  species  a  definite  percentage  of  the  food  is  retained 
for  growth  irrespective  of  the  size  of  the  individual. 

Rubner,2  in  apparent  ignorance  of  this  work  of  Dr.  Wilson, 
has  arrived  at  essentially  the  same  conclusions,  and  he  finds 
that  the  law  is  true  regarding  all  species  (horse,  calf,  sheep, 
pig,  dog,  cat,  rabbit)  except  man.  He  formulates  the  "law 
of  constant  energy  expenditure"  as  follows:     The  amount  of 

1  Rost:  "Arbeiten  aus  dem  kaiserlichen  Gesundheitsamte,"  1901,  xviii, 
206. 

2  Rubner:  "Das  Problem  der  Lebensdauer  und  seiner  Beziehung  zu  Wachs- 
tum  und  Ernahrung,"  1908. 


414  SCIENCE   OF   NUTRITION 

energy  {calories)  which  is  necessary  to  double  the  weight  of  the 
newborn  of  all  species  (except  man)  is  the  same  per  kilogram 
no  matter  whether  the  animal  grows  quickly  or  slowly.  To 
construct  one  kilogram  of  normal  body  substance  containing 
30  grams  of  nitrogen  and  1722  calories,  4808  calories  are  re- 
quired except  in  the  case  of  man,  where  six  times  that  amount 
is  needed.  This  is  almost  in  exact  agreement  with  the  experi- 
ments of  Wilson. 

The  same  principles  apply  to  the  growth  of  rats,  as  may  be 
seen  from  the  following,  calculated  from  the  results  of  Funk 
and  Macallum,1  who  fed  these  animals  during  twenty-eight 
days: 


Stunted  20 

Normal. 

Controls. 

Days. 

Number  of  rats 2 

2 

2 

Weight  in  grams  at  start .  .        29 

27-5 

27.0 

Growth  in  grams 40 

42 

65 

Available  calories  ingested.    1223 

1216 

1895 

Gain   in   grams    per    1000 

calories  ingested 32.7 

34-5 

34-3 

Calories  for  construction  of 

1  gram  new  tissue 30.6 

29.0 

29.1 

In  the  work  of  Hopkins2  different  sets  of  rats  were  given 
the  same  food  in  different  quantities,  and  the  following  table 
has  been  calculated  from  the  results  obtained  after  nine  days 
of  food  ingestion : 

Number  of  rats  used 12  14  18  15 

Calories  ingested  daily  per  100  grams  of 

rats,  live  weight 45  50  55  60 

Average  initial  weights,  grams 45.3  45.2  42.2  43.2 

Gain  in  grams  of  rats 8.8  10.3  11.1  12.8 

Gain  in  grams  per  1000  calories  ingested.  48  51  53  55 

Another  lot  of  rats  when  given  65  calories  per  hundred 
grams  live  weight  refused  to  eat  all  their  food.  It  is  of 
great  interest  that,  notwithstanding  the  restriction  of  the 
dietary  below  the  limits  set  by  the  appetite  in  some  of  the 
experiments,  yet  the  gain  in  the  weight  of  the  rats  is  nearly 

1  Funk,  C,  and  Macallum,  A.  Bruce:  "Journal  of  Biological  Chemistry," 
1915,  xxiii,  413. 

2  Hopkins:   "Journal  of  Physiology,"  1912,  xliv,  425. 


POOD  REQUIREMENT  DURING  THE  PERIOD  OF  GROWTH   415 

proportional  to  the  calories  in  the  dietary.  Evidently,  ample 
protein,  together  with  calcium  and  other  salts,  was  present  for 
the  construction  of  new  tissue  in  all  the  rats.  Aron1  has 
shown  that  when  growing  dogs  are  given  too  little  energy  in 
their  food,  the  skeleton  may  grow  and  the  weight  increase, 
though  the  caloric  content  of  the  animal  may  diminish. 

Rubner  finds  in  all  species  the  constant  retention  of  ap- 
proximately the  same  percentage  of  the  energy  ingested,  which 
averages  34.3  per  cent.,  except  in  the  case  of  man,  where  the 
energy  retained  for  growth  is  only  5.2  per  cent.  He  states 
that  40  per  cent,  of  the  energy  ingested  may  be  retained  for  the 
growth  of  pigs,  whereas  Dr.  Wilson  found  only  20  per  cent,  so 
retained.  This  is  because  the  pigs  in  the  latter  case  were 
given  skimmed  milk,  and  the  added  tissue  substance  was  found 
on  analysis  to  have  a  heat  value  of  only  866  calories  per  kilo- 
gram, instead  of  1722  as  assumed  by  Rubner. 

It  is  therefore  evident  that  while  it  requires  the  same  energy 
equivalent  to  construct  one  kilogram  of  new  substance  in 
young  animals,  the  percentage  of  energy  retained  for  growth 
may  depend  upon  the  amount  of  fat  in  the  diet. 

Rubner  states  that  if  the  requirement  for  energy  in  the 
various  animals  be  placed  at  100,  then  the  amount  of  energy  in 
the  food  actually  ingested  by  them  averages  202.  This  corre- 
sponds to  Dr.  Wilson's  computation  of  the  energy  ingested  by 
the  growing  pigs,  which  averaged  2100  calories  per  square 
meter  of  surface,  as  compared  with  a  normal  requirement  of 
1089.  Dr.  Wilson  explained  this  high  energy  requirement  as 
being  partly  due  to  growth  and  partly  to  the  extreme  activity 
of  the  little  animals.  A  human  infant  does  not  require  this 
large  excess  of  energy  in  his  food,  probably  because  he  is  kept 
warm  and  sleeps  much  of  the  time. 

Finally,  Rubner  has  calculated  that  the  quantity  of  energy 
metabolized  in  a  kilogram  of  living  cells  from  maturity  to  death 
is  the  same  in  different  animals,  except  in  the  case  of  man,  who 
again  occupies  an  exceptional  position. 

^ron:   "Biochemische  Zeitschrift,"  1910-11,  xxx,  207. 


41 6  SCIENCE   OF    NUTRITION 

This  is  represented  in  the  following  table: 


Body  Weight 
in  Kg. 

Length  of 

Life  in  Years 

after  Maturity. 

Calories  Produced 

per  Kg.  Adult 

Body  Substance. 

Man  .         

60. 

450- 
450. 

22. 

3- 

0.6 

60 

3° 
26 

9 
8 
6 

775.7/0 

169,900 

141,090 

Dog 

163,900 

223,800 

265,500 

Rubner  finds  that  among  the  animals  each  kilogram  of 
adult  body  substance  metabolizes  an  average  of  191,600 
calories  and  then  dies.  Man  alone  has  power  in  his  proto- 
plasm to  use  a  much  larger  share  of  energy  in  the  furtherance 
of  his  activities. 

Bunge1  has  recalled  the  relationship  between  rapidity 
of  growth  and  longevity,  as  orginally  suggested  by  Flourens 
in  1856.  This  writer  believed  that  if  the  time  of  reaching 
the  end  of  growth  be  multiplied  by  5,  the  average  term  of 
life  might  be  computed.  This  relationship  may  be  tabulated 
as  follows : 

TABLE  SHOWING  FLOURENS'  LAW  OF  LONGEVITY 


Time  in  Days 
from  Birth 
to  Double 

Birth-weight. 

Time  in 

Years  Until 

Full 

Growth. 

Deduced 
Average  Lon- 
gevity in 
Years. 

Maximum  Re- 
corded Lon- 
gevity in 
Years. 

Man 

Camel 

Horse 

Cow 

180 

60 

47 

'9* 

9 

20 
8 
5 
4 
4 
il 
2 

90-100 
40 

25 
15-20 

3° 
9-10 

10-12 

152-169 
100 

50 

Lion 

60 

Cat 

20 

Dog 

24 

Bunge  calls  attention  to  the  fact  that  a  horse  more  often 
lives  to  be  forty  than  a  man  to  be  a  hundred.     Either  the  law 

1  Bunge:   "Pfliiger's  Archiv,"  1903,  xcv,  606. 


FOOD   REQUIREMENT   DURING   THE    PERIOD    OF    GROWTH       417 

is  false,  or  man  is  a  too  early  victim  of  an  improper  heredity 
or  environment. 

Very  little  has  been  accomplished  upon  the  subject  of  the 
mineral  metabolism  of  growing  children,  so  the  following  work 
of  Jundell1  is  of  especial  interest.  Two  boys,  K.  and  N.,  were 
given  a  diet  during  ten  days  containing  2.9  grams  of  protein, 
2.7  grams  of  fat,  10.8  grams  of  carbohydrate,  and  in  all  81 
calories  per  kilogram  of  body  weight  daily.  The  mineral 
metabolism  as  calculated  per  kilogram  of  body  weight  daily 
was  as  follows: 


MINERAL  METABOLISM  OF  K.  (5|  YEARS  OLD,  WEIGHT  18.4  KG.) 
AND  OF  N.  H\  YEARS  OLD,  WEIGHT  23.1  KG.)  IN  GRAMS  PER 
KG.  PER  DAY 


Intake. 

Fec 

ES. 

Urine. 

Retention. 

K.           N. 

K. 

N. 

K. 

N. 

K. 

N. 

Total  ash 

0-747 

0.697 

0.134 

0.124 

0.469 

0.429 

+  O.144 

+  0.144 

P2O5 

0.144 

0.136 

0.049 

O.043 

0.064 

0.064 

+0.032 

+O.030 

CaO 

0.060 

0.076 

0.050 

0.042 

0.007 

0.045 

+0.003 

+0.029 

MgO 

O.071 

0.065 

0.047 

O.041 

O.OIO 

0.008 

+  0.014 

+0.016 

KoO 

0.141 

0.136 

0.012 

0.013 

0.116 

0.106 

+O.OI2 

+0.018 

Na20 

Q-345 

0.224 

O.OII 

0.012 

0.104 

0.103 

+  0.231 

+0.110 

CI 

o.344 

0.324 

0.003 

0.004 

0.309 

0.292 

+  0.032 

+  0.028 

It  may  be  calculated  from  this  table  that  the  older  boy 
took  1.8  grams  of  calcium  oxid  in  his  food  daily  and  retained 
about  0.07  gram.  If  the  intake  had  been  solely  in  the  form 
of  cows'  milk,  not  far  from  a  liter  would  have  been  required. 
One  of  the  most  important  questions  of  the  time  concerns  the 
determination  of  the  quantity  of  salts  in  the  food  necessary  to 
prevent  malnutrition  in  children,  and  it  would  be  well  to  know 
the  quantity  of  cows'  milk  which  should  be  prescribed  in  the 
daily  diet  of  children  in  order  to  satisfy  the  mineral  require- 
ments for  normal  growth. 

For  metabolism  in  youth,  see  page  559. 

jundell:   ''Nordiskt  Medicinskt  Arkiv,"  1914,  xlvii,  Abth.  2,  1. 


27 


CHAPTER  XV. 

METABOLISM  IN  ANEMIA,  AT  HIGH  ALTITUDES,  IN 
MYXEDEMA,  AND  IN  EXOPHTHALMIC  GOITER 

In  man  one-thirteenth  part  of  the  body  weight  is  carried  as 
blood  to  the  lungs  at  least  every  minute  and  there  exposed  for 
a  period  of  two  seconds  to  the  action  of  the  alveolar  air.  The 
blood  in  the  capillaries  of  the  lungs  may  be  estimated  as  a  film 
o.oi  millimeter  in  thickness  and  150  square  meters  in  area,  or 
nearly  a  hundred  times  the  area  of  the  surface  of  the  body. 
Zuntz  estimates  the  combined  thickness  of  the  alveolar  wall 
and  capillary  wall  at  0.004  mm-  This  is  the  total  distance 
separating  the  alveolar  air  from  the  blood.  The  gaseous  ex- 
change between  air  and  blood  is  thus  readily  made  possible. 

In  an  experiment  by  Henriques1  four  different  deter- 
minations were  made  upon  an  anesthetized  dog:  (1)  The  rate 
of  flow  of  blood;  (2)  the  carbon  dioxid  and  oxygen  content  of 
the  venous  blood  in  the  right  heart;  (3)  the  quantity  of  the 
same  gases  in  the  blood  of  the  femoral  artery,  that  is,  after  the 
lungs  had  been  traversed,  and  (4)  the  extent  of  the  gaseous 
exchange  in  the  lungs  was  measured.  The  rapidity  of  the 
blood  flow  was  1806  c.c.  in  three  minutes.  The  following 
calculations  show  that  no  oxidation  took  place  in  the  lungs  or 
in  the  blood,  and  in  publishing  these  results  Henriques  recants 
a  contrary  opinion  previously  held  by  him : 

CO2.  o2. 

c.c.  c.c.  R.  Q. 

In  100  c.c.  blood  of  right 

heart 44-34  2-74 

In  100  c.c.  blood  of  femoral 

artery 31.55  15-25 

Difference —12.79  +12.51 

Calculated  from    1806  c.c. 

blood  flow 231  226  1.02 

Respiration  experiment 

(three  minutes) 250  239  1.05 

Difference 8  per  cent.  5  per  cent. 

1  Henriques:   "Biochemische  Zeitschrift,"  1915,  lxxi,  481. 

418 


METABOLISM    IN   ANEMIA  419 

The  differences  are  within   the  limits  of  experimental  error. 
It  is  evident  that  the  place  of  oxidation  is  in  the  tissues  (see 

P-32)- 

Complete  deprivation  of  oxygen  results  in  asphyxiation 

and  death.     The  question  arises,  Will  there  be  any  effect  upon 

metabolism  if  the  oxygen  supply  for  the  body  be  reduced? 

Such  a  reduction  of  oxygen  available  for  the  tissues  might 

be  brought  about  by  bloodletting,  anemia,  carbon-monoxid 

poisoning,  by  life  on  high  mountains,  or  in  balloons  at  high 

altitudes,  or  in  pneumatic  cabinets  at  reduced  pressure,  or  by 

the  artificial  restriction  of  the  free  influx  of  atmospheric  air 

into  the  lungs.     Any  of  these  methods  if  carried  beyond  a 

certain  point  is  known  to  produce  death. 

It  was  noted  by  Lavoisier  and  confirmed  by  Regnault  and 
Reiset  that  the  respiration  of  pure  oxygen  did  not  increase  the 
metabolism.  Liebig  was  convinced  that  atmospheric  pressure 
was  without  influence,  for  it  was  evident  to  him  that  life  at  the 
sea-level  was  of  the  same  character  as  on  high  mountains.  In 
confirmation  of  these  principles  Zuntz1  has  definitely  shown  that 
if  air  rich  in  oxygen  be  respired,  there  is  an  increased  oxygen 
absorption  lasting  for  about  one  minute,  and  then  the  normal 
quantity  is  absorbed.  The  primary  increase  in  the  quantity 
of  oxygen  absorbed  is  due  to  the  rilling  of  the  lungs  with  oxygen 
and  a  further  saturation  of  the  blood  with  it,  processes  which 
are  without  effect  on  tissue  metabolism.  There  is  apparently 
no  retention  of  such  oxygen  within  the  cells  of  the  organism. 

However,  Hill  and  Flack2  show  that  in  the  fatigue  of  athletes 
oxygen  inhalation  increases  the  lasting  power  and  decreases  the 
fatigue,  probably  by  maintaining  or  restoring  the  vigor  of  the 
heart.  They  believe  that  the  fatigue  which  follows  an  athletic 
feat  is  mainly  cardiac  in  origin  and  due  to  want  of  oxygen. 

Pfluger3  first  showed  that  frogs  could  live  for  a  long  period 
in  an  atmosphere  which  was  free  from  oxygen  when  they  were 
maintained  at  a  temperature  of  o°.     After  five  hours  they 

1  Zuntz:    "Archiv  fur  Physiologic,"  1003,  Suppl.,  p.  492. 

2  Hill  and  Flack:    "Journal  of  Physiology,"  1909,  xxxviii,  p.  xxviii. 

3  Pfluger:    "Pfluger's  Archiv,"  1875,  x,  313. 


420  SCIENCE    OF   NUTRITION 

were  capable  of  movement,  and  after  seventeen  hours,  although 
apparently  dead,  they  could  be  revived  when  placed  in  the  air. 
Fletcher  and  Hopkins1  have  found  traces  of  lactic  acid  in 
normal  resting  frog's  muscle,  and  also  traces  after  a  series  of 
muscular  contractions  which  were  induced  in  an  atmosphere 
of  oxygen;  but  they  found  lactic  acid  in  large  quantity  in  the 
muscle  if  the  contractions  were  brought  about  under  anaerobic 
conditions. 

Lesser2  has  placed  frogs  in  an  ice  calorimeter  and  filled  the 
chamber  in  which  they  lived  first  with  air  and  then  with  hydro- 
gen. When  living  in  air  the  animals  produced  more  heat  and 
only  half  as  much  carbon  dioxid  as  they  did  when  they  lived  in 
hydrogen  gas.  In  the  air  each  milligram  of  carbon  dioxid 
exhaled  corresponded  to  a  production  of  4.5  small  calories;  in 
hydrogen,  to  only  1.6  calories.  Hence  the  processes  taking 
place  in  the  two  cases  could  not  have  been  the  same.  The 
anaerobic  carbon  dioxid  production  could  not  have  been  at  the 
expense  of  oxygen  stored  in  the  tissues  of  the  frog  or  the  heat 
production  per  unit  of  carbon  dioxid  exhaled  would  have  been 
the  same  as  in  air,  instead  of  being  only  35  per  cent,  as  much. 
The  processes  involved  in  this  case  can  only  be  conjectured. 
It  has  already  been  stated  that  ascaris,  an  anaerobic  inhabitant 
of  the  intestine,  may  convert  glycogen  into  fatty  acid  with  the 
elimination  of  carbon  dioxid  and  the  evolution  of  heat.  (See 
p.  305.)  Similar  processes  might  take  place  in  the  anaerobic 
frog. 

Lesser3  has  further  shown  that  the  quantity  of  oxygen 
absorbed  by  a  frog  at  150  is  independent  of  the  pressure  of 
oxygen  in  the  atmosphere  until  a  percentage  of  3.3  of  oxygen 
is  reached.  At  this  point  the  respiratory  quotient  was  1.02. 
When  1.8  per  cent,  of  oxygen  was  present  the  quantity  of 
oxygen  absorbed  decreased  to  one-third  the  normal  and  the 
respiratory  quotient  rose  to  2.40,  indicating  anaerobic  cleav- 
age of  the  food  materials  with   the  production   of  carbon 

1  Fletcher  and  Hopkins:   "Journal  of  Physiology,"  1907,  xxxv,  247. 

2  Lesser:   "Zeitschrift  fiir  Biologie,"  1908,  li,  287. 

3  Lesser:   "Biochemische  Zeitschrift,"  1914,  lxv,  400. 


METABOLISM   IN   ANEMIA  42 1 

dioxid.  After  eight  hours  of  this  treatment  the  frog  became 
paralyzed. 

According  to  Zuntz,1  any  anemic  condition  which  results 
in  the  production  of  lactic  acid  makes  demands  on  the  glycogen 
reserves  of  the  body,  so  that  sugar  may  rise  abnormally  in 
the  blood,  and  both  sugar  and  lactic  acid  appear  in  the 
urine. 

Muscular  exertion  in  man  leads  to  an  increase  in  the  quan- 
tity of  lactic  acid  in  both  blood2  and  urine,3  due,  in  all  probabil- 
ity, to  slight  local  anemia  in  the  muscles.     (See  p.  322.) 

The  consideration  of  the  subject  of  subnormal  oxygen  sup- 
ply may  first  be  considered  in  connection  with  bloodletting, 
which  produces  an  artificial  anemia.  Bauer,4  in  Voit's  labor- 
atory, was  the  first  to  study  this  systematically,  and  found 
that  the  immediate  result  of  bloodletting  in  the  dog  was  an 
increased  protein  metabolism,  but  that  the  carbon  dioxid 
elimination  was  unchanged;  18  to  27  per  cent,  of  the  total 
blood  in  the  body  was  removed  in  these  experiments. 

Hawk  and  Gies5  confirm  the  reports  of  a  higher  protein 
metabolism  after  bloodletting. 

Finkler,6  in  Pfliiger's  laboratory,  withdrew  one-third  of  the 
total  blood  from  a  dog,  thereby  reducing  the  rapidity  of  blood- 
flow  in  the  femoral  artery  by  one-half,  and  yet  there  was  no 
change  in  the  quantity  of  oxygen  absorbed,  and,  therefore,  of 
the  quantity  of  the  carbon  dioxid  exhaled.  Finkler  noted,  how- 
ever, that  the  quantity  of  oxygen  in  the  venous  blood  grew 
constantly  less  after  repeated  bleedings.  This  indicates  the 
interrelation  between  the  oxygen  supply  and  the  needs  of  the 
tissues.  Under  ordinary  circumstances  there  are  20  volumes 
per  cent,  of  oxygen  in  the  arterial  blood,  of  which  12  volumes 
per  cent,  may  return  as  an  unused  excess  to  the  right  heart. 

1  Zuntz:  ''Die  Kraftleistung  des  Tierkorpers,"  Festrede,  Berlin,  1908,  p.  18. 

2  Fries:    "Biochemische  Zeitschrift,"  1911,  xxxv,  368. 

3Spiro:      "Zeitschrift  fur  physiologische  Chemie,"   1877,  i,   in;   Ryffel: 
"Journal  of  Physiology,"   190Q-10,  xxxix,  p.  xxix. 
4  Bauer:    "Zeitschrift  fur  Biologie,"  1872,  viii,  567. 
6  Hawk  and  Gies:   "American  Journal  of  Physiology,"  1904,  xi,  226. 
6  Finkler:    "Pfliiger's  Archiv,"  1875,  x,  368. 


42  2  SCIENCE   OF   NUTRITION 

Repeated  bleedings  by  Finkler  reduced  this  percentage  in 
venous  blood  from  11.80  per  cent,  to  8.80,  4.06,  and  2.71  per 
cent.  The  carbon  dioxid  content  of  the  blood  remained  un- 
changed. This  decrease  in  the  oxygen  content  of  the  blood 
may  stimulate  both  the  heart  and  respiration  to  compensatory 
activity,  although  nothing  resembling  asphyxia  be  present. 
While  the  total  heat  production  is  unchanged  in  anemia 
following  bloodletting  (except  as  influenced  by  increased 
cardiac  and  respiratory  activity),  still  it  is  evident  from  the 
diminution  of  oxygen  present  in  venous  blood  that  there  would 
not  be  a  sufficient  supply  of  oxygen  to  provide  for  a  largely 
increased  metabolism.  Hence  the  anemic  organism  is  in- 
capable of  great  muscular  work  without  quick  exhaustion  ac- 
companied by  rapid  respiration  and  heart-beat.  These  latter 
are  further  efforts  of  compensation  for  the  decrease  in  the 
oxygen-carrying  elements  of  the  blood. 

The  removal  of  blood  from  a  dog,  followed  by  the  trans- 
fusion of  an  equal  quantity,  has  no  effect  upon  metabolism,1 
although  if  an  artificial  plethora  be  induced  by  the  intravenous 
injection  of  fresh  blood  into  a  normal  animal,  the  metabolism 
is  slightly  increased,  a  result  which  is  probably  due  to  in- 
creased heart  action.2 

After  bloodletting  of  any  considerable  magnitude,  lactic 
acid  and,  it  is  reported,  a  small  amount  of  sugar  appear  in 
the  urine.  Thus  Araki3  found  lactic  acid  in  the  urine  of 
rabbits  which  had  been  bled.  He  also  found  lactic  acid  in  the 
urine  of  rabbits  which  had  been  exposed  to  the  action  of 
rarefied  air,  and  he  found  lactic  acid  and  glucose  in  the  urine 
of  animals  the  oxygen-carrying  capacity  of  whose  blood  had 
been  diminished  through  the  respiration  of  carbon  monoxid. 
It  should  be  noticed  in  passing  that  wherever  lactic  acid  is 
formed  in  the  organism  there  is  a  concomitant  rise  in  protein 
metabolism.  Since  this  lactic  acid  is  a  derivative  of  glucose, 
its  non-combustion  may  raise  the  protein  metabolism  to  a 

1  Pembrey  and  Giirber:  "Journal  of  Physiology,"  1894,  xv,  449. 
2Hari:    "Biochemische  Zeitschrift,"  1911,  xxxiv,  in;  1912,  xliv,  1. 
8  Araki:    "Zeitschrift  fur  physiologische  Chemie,"  1894,  xix,  424 


METABOLISM    IN   ANEMIA  423 

higher  level,  just  as  is  the  case  when  sugar  remains  unburned 
in  diabetes. 

In  experimental  anemias  the  hemoglobin  content  of  the 
blood  of  rabbits1  or  dogs2  may  be  reduced  to  20  per  cent,  of 
the  normal  amount,  with  indications  of  only  slight  changes  in 
the  intensity  of  the  oxidative  processes,  and  these  are  usually 
in  the  direction  of  slight  increases.  Such  increases  one  may 
interpret  as  being  derived  from  the  rise  in  protein  metabolism 
and  as  due  to  stimulation  of  the  cells  by  lactic  acid  (see  p.  298). 

Another  fact  which  has  been  observed  by  Lewinstein3  is 
that  when  rabbits  are  kept  in  a  bell-jar  at  a  barometric  pres- 
sure of  300  to  400  mm.  (corresponding  to  5000  to  7500  meters 
above  sea-level)  they  die  on  the  second  or  third  day,  and 
autopsy  reveals  extreme  fatty  infiltration  of  heart,  liver, 
kidney,  and  diaphragm.  These  animals  took  no  food.  The 
cause  of  this  fatty  change,  in  the  present  writer's  opinion,  was 
the  lessened  combustion  of  sugar  or  its  derivative,  lactic  acid, 
which  always  induces  an  abnormal  deposit  of  fat  in  any  sugar- 
hungry  cells  (p.  490). 

Kohler4  artificially  compressed  the  trachea  of  rabbits  by 
tying  a  lead  wire  around  it.  The  animals  recovered  from  the 
operation  and  lived  for  four  weeks  in  a  condition  of  dyspnea. 
Appetite,  weight,  urine,  and  body  temperature  remained  nor- 
mal almost  until  the  end.  The  dyspnea  was  apparently  in- 
sufficient to  affect  the  metabolism.  Increased  respiration 
and  heart  activity  were  effectual  efforts  at  compensation,  so 
that  there  was  no  lack  of  oxygen  in  the  animals.  However, 
the  altered  pressure  in  the  lungs  and  the  continued  dyspnea 
brought  about  a  condition  of  stasis  of  which  the  animal  died. 
The  secondary  alterations  were  acute  and  wide-spread,  and 
were  hyperemia  of  the  lungs,  vesicular  and  intralobular 
emphysema  of  the  lungs,  and  hypertrophy  of  both  sides  of  the 
heart. 

1  Eberstadt:   "Archiv  fur  exp.  Path,  und  Pharm.,"  1913,  lxxi,  329. 

2  Roily:    "Deutsches  Archiv  fur  klinische  Medizin,"  1914,  cxiv,  605. 

3  Lewinstein :    "Pfluger's  Archiv,"  1897,  lxv,  278. 

4  Kohler:    "Archiv  fur  exp.  Path,  und  Pharm.,''  1877,  vii,  1. 


424 


SCIENCE   OF   NUTRITION 


Pettenkofer  and  Voit1  observed  the  metabolism  in  an  acute 
case  of  leukocythemia  of  four  years'  duration,  and  at  a  time 
four  months  before  the  death  of  the  patient.  There  was  one 
white  to  every  three  red  blood-corpuscles,  a  high  degree  of 
anemia,  and  great  physical  weakness.  The  metabolism  was 
exactly  the  same  as  in  a  normal  resting  man  living  under  the 
same  dietary  conditions. 

Magnus-Levy  states  that,  rightly  interpreted,  these  experi- 
ments of  Voit  indicate  an  increased  metabolism.  He2  found 
an  increased  metabolism  in  a  case  of  severe  pernicious  anemia. 
Grafe3  reports  a  large  increase  in  metabolism  in  leukemia. 
Roily,4  however,  states  that  in  chlorosis  and  in  mild  anemias 
there  is  no  increase  in  metabolism  in  human  beings. 

Meyer  and  Du  Bois5  made  calorimetric  observations  upon 
5  patients  suffering  from  anemia.  Direct  and  indirect  calor- 
imetry  agreed  within  3  per  cent,  and  the  respiratory  quotients 
ranged  within  the  normal  limits.  The  following  table  epitom- 
izes their  results: 

METABOLISM   IN   ANEMIA   IN   MAN 


Case  I. 
Case  II. 
Case  III. 

Case  IV. 
Case  V. 


Type. 


Splenic 

Pernicious 

Pernicious:    transverse 

myelitis 

Pernicious 

Pernicious 


Hemoglobin  in 

Blood  in  Per 

Cent. 


25 
20 

23-21 

44 
40 


Increase  in 

Heat  Production 

Above  Basal 

in  Per  Cent. 


24-19 

33-7 
2 
6 


These  results  show  an  increased  metabolism  in  pernicious 
anemia  which  is  especially  pronounced  when  the  hemoglobin 
content  of  the  blood  falls  to  20  per  cent,  of  the  normal. 

In  Case  III  the  legs  were  wasted  and  atrophic  and  could  no 

1  Pettenkofer  and  Voit:   "Zeitschrift  fur  Biologie,"  1869,  v,  319. 

2  Magnus-Levy:   "Zeitschrift  fiir  klinische  Medizin,"  1906,  lx,  179. 

3  Grafe:   "Deutsches  Archiv  fiir  klinische  Medizin,"  1911,  cii,  406. 

4  Roily:  Loc.  cit. 

6  Meyer,  A.  L.,  and  Du  Bois:  "Archives  of  Internal  Medicine,"  1916,  xvii, 
965- 


METABOLISM   IN   ANEMIA  425 

longer  be  used.  Of  itself,  this  condition  would  have  lowered 
the  metabolism. 

Meyer  calculated  for  Case  II  that  there  were  3.7  c.c.  of 
oxygen  in  100  c.c.  of  arterial  blood.  If  the  patient  had  had 
a  normal  heart-beat  of  70  per  minute  with  an  output  of  blood 
of  50  c.c.  per  beat,  130  c.c.  of  oxygen  would  have  been  carried 
to  the  tissues  per  minute.  In  fact,  252  c.c.  of  oxygen  were 
absorbed  by  the  patient  each  minute  and  his  pulse-rate  was 
1 01.  To  have  supplied  enough  oxygen  for  tissue  respiration 
his  output  of  blood  per  heart-beat  must  have  been  at  least 
66  c.c. 

Another  patient  with  lymphatic  leukemia  had  a  very  high 
metabolism  which  was  scarcely  affected  by  vigorous  #-ray 
therapy,  although  the  lymphocytes  were  greatly  diminished 
in  number.1 

The  characteristic  optical  properties  of  human  hemoglobin, 
its  power  to  combine  with  between  1.33  to  1.35  c.c.  of  carbon 
monoxid  gas  per  gram  of  substance,  and  its  iron  content  of  0.33 
to  0.34  per  cent.,  are  always  constant,  both  normally  and  in 
diseases  such  as  polycythemia,  pernicious  anemia,  chlorosis, 
scurvy,  and  pseudoleukemia.  This  important  fact,  which 
shows  that  hemoglobin  is  not  itself  chemically  changed  in 
anemia,  was  demonstrated  by  Butterfield.2 

In  emphysema  of  the  lungs  in  man  determinations  by 
Geppert  and  by  Speck3  have  shown  that  the  respiratory 
exchange  of  gases  was  entirely  within  normal  limits. 

Carpenter  and  Benedict4  have  found  the  metabolism  of 
a  man  in  whom  the  left  lung  was  entirely  obliterated  to  be 
unchanged  from  the  normal. 

It  is  evident  from  these  various  citations  that  the  general 
oxidation  of  the  body  is  normally  maintained  in  anemia  and  in 
pulmonary  disease,  provided  the  disturbances  are  not  of 
extreme  intensity. 

1  Means  and  Aub,  unpublished. 

2  Butterfield:    "Zeitschrift  fur  physiologische  Chemie,"  1909,  lxii,  173. 

3  Cited  by  Jaquet:    "Ergebnisse  der  Physiologie,"  1903,  ii,  I,  562. 

4  Carpenter  and  Benedict :  "Journal  of  Biological  Chemistry,"  1909,  vi,  p.  xv. 


426  SCIENCE    OF   NUTRITION 

The  constantly  increasing  use  of  mountain  air  as  a  recuper- 
ative force  for  the  worn-out  individual  leads  to  the  inquiry 
whether  the  metabolism  at  high  altitudes  is  different  from  that 
at  the  sea-level.  For  knowledge  of  this  sort  we  are  principally 
indebted  to  Zuntz  and  his  pupils.  The  study  of  the  subject 
may  be  taken  up  by  using  three  different  methods:  First,  the 
pneumatic  cabinet;  second,  balloon  ascensions;  third,  moun- 
tain ascents. 

The  pressure  of  the  atmosphere  varies  with  the  height  from 
the  sea-level  as  appears  in  the  following  table: 


Altitude. 

Barometer 

Meters. 

Feet. 

Miles. 

in  Mm.  Hg. 

0 

0 

0. 

760 

1000 

3,28i 

0.6 

670 

2000 

6,562 

1.2 

592 

3000 

9,843 

1.9 

522 

4000 

13,124 

2-5 

460 

5000 

16,405 

3-i 

406 

6000 

19,686 

3-7 

358 

7000 

22,967 

4.4 

316 

8000 

26,248 

5-° 

297 

9000 

29,S29 

5-6 

In  a  celebrated  balloon  ascension  made  by  Tissandier  and 
two  companions  in  1875  only  Tissandier  lived  to  tell  the 
following  tale: 

At  a  height  of  7000  meters  Tissandier  is  unable  to  make  the 
effort  to  remove  his  gloves  from  his  pocket.  All  breathe 
oxygen.  The  temperature  is  —  1 1°.  Sivel  throws  ballast.  At 
7500  meters  the  condition  of  torpor  is  extraordinary,  but  there 
is  no  suffering.  The  arms  cannot  be  moved  to  reach  for  the 
oxygen  tube.  At  280  mm.  barometric  pressure  Tissandier 
wishes  to  call  out  that  the  level  of  8000  meters  has  been  passed, 
but  cannot  speak.  Consciousness  is  then  lost.  The  height 
of  263  mm.  barometric  pressure  is  reached  before  the  balloon 
begins  to  descend  and,  on  recovery  of  consciousness,  Tissandier 
finds  that  his  two  companions  are  dead. 

In  1909  the  Duke  of  Abruzzi,  with  several  companions, 
ascended  to  a  height  of  7500  meters  (=  24,600  ft,  =  4.7 
miles  =  312  mm.  Hg.)  in  the  Himalayas,  and  although  the 


METABOLISM    IN   ANEMIA  427 

physical  conditions  were  extremely  trying,  they  suffered  no 
serious  physiologic  inconvenience.  Douglas,  Haldane.  Hen- 
derson, and  Schneider1  point  out  that  this  immunity  was 
acquired  by  prior  acclimatization  during  two  months  of 
residence  at  an  altitude  of  17,000  feet.  The  ascent  of  Mt. 
Everest,  the  highest  mountain  in  the  world  (8840  meters 
=  29,000  feet  ==  5.5  miles),  though  perhaps  physically  un- 
attainable, may  not  be  physiologically  impossible. 

The  relative  composition  of  the  atmosphere  is  the  same  at 
all  distances  from  the  earth's  surface.  Durig  and  Zuntz2  find 
that  the  atmosphere  at  a  height  of  2900  meters  contains  carbon 
dioxid  0.03  per  cent.,  nitrogen  79.11  per  cent.,  and  oxygen 
20.86  per  cent.,  whereas  at  an  altidude  of  4600  meters  it  con- 
tains carbon  dioxid  0.03  per  cent.,  nitrogen  79.10  per  cent., 
oxygen  20.87  Per  cent.  These  are  values  practically  identical 
with  each  other  and  with  those  determined  at  sea-level. 

Fraenkel  and  Geppert3  placed  a  dog  which  had  fasted 
seven  days  under  the  influence  of  greatly  diminished  at- 
mospheric pressure  and  found  an  increased  protein  metabolism 
which  continued  on  the  second  and  third  days.  They  also 
suspected  the  presence  of  products  of  incomplete  combustion 
in  the  urine.     These  results  accord  with  Araki's  investigations. 

Von  Terray4  finds  no  change  in  the  respiratory  activity  of 
dogs  in  air  containing  between  87  and  10.5  per  cent,  of  oxygen. 
When  10.5  per  cent,  of  oxygen  is  present  an  increased  respira- 
tory activity  commences.  With  5.25  per  cent,  of  oxygen  there 
is  every  indication  of  lack  of  oxygen  for  the  tissues,  and  the 
elimination  of  lactic  acid  in  the  urine  is  pronounced.  The 
quantity  of  lactic  acid  eliminated  was  greatest  after  the  res- 
piration of  an  atmosphere  containing  3  per  cent,  of  oxygen. 
The  quantities  obtained  were  1.206,  1.860,  2.176,  2.300,  2.352, 
2.663,  3-020>  and  3.686  grams  of  lactic  acid  in  twenty-four 

1  Douglas,  Haldane,  Henderson,  and  Schneider:  "Transactions  of  the 
Royal  Society,"  191 2,  Series  B,  cciii,  185. 

2  Durig  and  Zuntz:    "Archiv  fur  Physiologie,"  1904,  Suppl.,  p.  421. 

3  Fraenkel  and  Geppert:  "Ueber  die  Wirkungen  der  verdiinnten  Luft," 
1883. 

4  von  Terray:   "Pfliiger's  Archiv,''  1896,  lxv,  440. 


428  SCIENCE   OF   NUTRITION 

hours.  In  these  cases  we  again  see  the  analogy  of  the  metab- 
olism to  that  already  cited  as  having  been  discovered  by 
Araki  after  bloodletting  in  rabbits. 

L.  Zuntz1  found  that  when  he  respired  in  a  pneumatic  cab- 
inet at  an  atmospheric  pressure  of  448  mm.  of  mercury  there 
was  no  change  in  his  respiratory  metabolism  as  compared  with 
the  normal.     The  results  may  be  tabulated  as  follows: 

Per  Cent.  O2  Respired  per  Minute. 

in  Axr.  Pressure  in  Mm.  Hg.        O2  CC  CO2  in  C.C. 

21  758  mm.  231.25  200.15 

12  448  mm.  238.7  213. 1 

This  latter  experiment  was  done  at  a  pressure  correspond- 
ing to  a  mountain  height  of  4500  meters.  He  also  showed  that 
variations  in  atmospheric  pressure  within  the  above  limits  had 
no  effect  on  the  metabolism  during  muscular  exercise. 

This  work  was  repeated  by  Hasselbalch  and  Lindhard2 
in  an  experiment  which  lasted  twenty-six  days.  During 
fourteen  days  a  man  remained  in  a  pneumatic  cabinet  at  an 
atmospheric  pressure  of  455  mm.  The  consumption  of  oxygen 
and  the  urinary  ammonia  and  amino-acids  were  unaffected  by 
this  influence. 

Von  Schrotter  and  Zuntz3  made  two  balloon  ascents  to 
heights  of  4560  and  5160  meters.  Zuntz  showed  an  increased 
oxygen  absorption  of  7  per  cent,  above  that  at  sea-level.  In 
the  case  of  Von  Schrotter  the  increase  was  slight  except  during 
one  interval  of  shivering,  when  a  20  per  cent,  increase  was 
recorded.  The  authors  attributed  the  slight  rise  in  the  metab- 
olism to  the  increased  work  done  by  the  respiratory  muscles. 
During  the  higher  ascent  sugar  appeared  in  the  urine  of  Zuntz, 
indicating  incomplete  oxidation. 

A  research  of  Zuntz4  on  the  subject  of  mountaineering 
describes  how  he  and  Durig  ascended  to  the  Col  d'Olen  (2900 
meters),  and,  having  remained  there  for  a  week,  passed  up- 

1  Loewy  and  Zuntz:   "Pfliiger's  Archiv,"  1897,  lxvi,  477. 

2  Hasselbalch  and  Lindhard:  "Biochemische  Zeitschrift,"  1914,  Ixviii, 
265  and  295. 

3  von  Schrotter  and  Zuntz:    "Pfliiger's  Archiv,"  1902,  xcii,  479. 

4  Durig  and  Zuntz:   "Archiv  fur  Physiologie,"  1904,  Suppl.,  p.  417. 


METABOLISM   IN   ANEMIA  429 

ward  to  a  hut  (4560  meters)  constructed  near  the  summit  of 
Monte  Rosa,  the  highest  mountain  of  the  Alps  after  Mont 
Blanc.  They  lived  in  this  hut  two  weeks  and  a  half.  The 
height  of  the  barometer  was  443  millimeters,  which  indicates  a 
quantity  of  oxygen  amounting  to  12.2  per  cent,  of  an  atmos- 
phere. On  the  Col  d'Olen  there  was  no  increase  in  their  metab- 
olism when  they  were  resting,  and  there  was  no  increase  in  the 
requirement  of  energy  necessary  to  accomplish  one  kilogram- 
meter  of  work.  This  agrees  with  the  results  of  Biirgi  else- 
where mentioned  (p.  332).  At  the  higher  level,  near  the  sum- 
mit of  the  mountain,  the  resting  metabolism  increased  at  once 
and  permanently  to  the  extent  of  15  per  cent.  Zuntz  during 
a  former  sojourn  had  noted  an  increase  of  44  per  cent,  in  his 
metabolism  when  on  the  mountain.  Exposure  to  the  sun- 
light was  almost  without  effect  on  the  metabolism.  The 
increased  metabolism  was  not  due  to  cold,  for  it  was  present 
when  the  individual  was  in  a  warm  bed  in  the  hut.  At  sea- 
level  the  energy  equivalent  of  3  kilogrammeters  is  liberated 
in  the  body  in  order  to  lift  1  kilogram  of  body  substance  1 
meter  high.  Here  on  the  snow-fields  of  Monte  Rosa  Durig 
required  the  equivalent  of  4.0  to  4.8,  Zuntz  5.3  to  6.8  kilo- 
grammeters of  energy  to  accomplish  1  kilogrammeter  of 
work.  This  agrees  with  a  former  experiment  of  Zuntz  when 
he  was  living  in  the  same  locality,  in  which  he  found  the  in- 
creased metabolism  necessary  to  effect  1  kilogrammeter  of 
work  in  climbing  was  70  per  cent,  above  the  requirement  for 
the  same  work  at  sea-level. 

Hasselbalch  and  Lindhard,1  while  noting  that  the  ultra- 
violet rays  of  the  sun  reduce  the  frequency  and  increase  the 
depth  of  respiration,  find  that  exposure  to  the  effect  of  such 
rays  in  the  high  Alps  (Brandenburger  Hut,  3290  meters)  has 
no  effect  upon  the  metabolism  (see  p.  150). 

Not  only  is  the  metabolism  necessary  to  accomplish  work 
greater  on  high  mountains  than  at  sea-level,  but  the  capacity 

1  Hasselbalch  and  Lindhard:  "Skan.  Archiv  fur  Physiologie,"  1911,  xxv, 
361. 


430  SCIENCE   OF   NUTRITION 

for  work  is  greatly  reduced.  Schumburg1  found  that  he  could 
accomplish  a  maximum  of  999  kilogrammeters  of  work  in  one 
minute  in  Berlin,  619  when  on  the  Monte  Rosa  glacier,  and 
only  354  kilogrammeters  when  he  was  on  the  top  of  the 
mountain.  The  limit  of  work  on  Monte  Rosa  was,  there- 
fore, one-third  what  could  be  accomplished  in  Berlin, 
probably  on  account  of  the  accumulation  of  imperfectly 
oxidized  products  of  metabolism,  which  reduces  the  muscular 
power.2 

Durig  and  Zuntz,  Mosso,  and  others  have  found  their  res- 
piration to  be  distinctly  of  the  Cheyne-Stokes  character  after  a 
return  to  the  hut  subsequent  to  exercise  in  the  higher  Alps. 
They  found  that  when  they  were  on  Monte  Rosa  a  temporary 
oppression  resulted  if  their  respiration  was  partly  hindered — 
as  in  the  case  of  lacing  their  boots.  Also  strict  attention  to  a 
definite  task  might  reduce  the  respiratory  activity  to  such  an 
extent  that  anemia  of  the  brain,  accompanied  by  dizziness, 
readily  ensued. 

In  1 9 1 1  the  Anglo-American  Pike's  Peak  Expedition,  consist- 
ing of  Douglas,  Haldane,  Yandell  Henderson,  and  Schneider,3 
spent  several  weeks  on  the  summit  of  Pike's  Peak  with  a 
view  to  making  a  thorough  study  of  physiologic  adaptation 
to  low  atmospheric  pressures.  The  altitude  of  Pike's  Peak  is 
4290  meters  (14,100  feet),  which  contrasts  with  the  altitude  of 
4560  meters  at  which  the  laboratory  on  Monte  Rosa  is  located. 
Pike's  Peak,  however,  differs  from  Monte  Rosa  in  having  a 
summit  which  in  summer  time  is  almost  free  from  snow,  in 
facility  of  access  by  means  of  a  cogwheel  railway  and  in  the 
possession  of  a  very  comfortable  hotel.  The  distance  from 
Manitou  to  the  summit  is  16.3  kilometers  (8.9  miles)  by  the 
cog-railway  and  the  difference  in  altitude  between  the  two 
localities  is  2220  meters  (7485  feet).  Robinson,  the  resident 
manager  of  the  hotel,  has  resided  six  months  each  year  for 

1  Schumburg  and  Zuntz:    "Pfliiger's  Archiv,"  1896,  lxiii,  488. 

2  Lee:   Fatigue,  "The  Harvey  Lectures,"  1905-06,  p.  169. 

3  Douglas,  Haldane,  Henderson,  and  Schneider:  "Transactions  of  the 
Royal  Society,"  1912,  Series  B,  cciii,  185. 


METABOLISM   IN   ANEMIA  43 1 

seventeen  years  on  the  summit  and  holds  the  record  for  the 
most  rapid  ascent  of  the  peak,  having  accomplished  it  in  two 
hours  and  thirty-one  minutes.  This  means  walking  at  the 
rate  of  6.5  kilometers  (3.5  miles)  per  hour  and  ascending  at  the 
rate  of  906  meters  (2974  feet)  during  the  same  interval. 
Since  the  body  weight  was  70  kilograms  the  hourly  heat 
production  might  have  been  (see  p.  327): 

Kgm.  Calories. 

For  lifting  the  body  weight  (70  X  906  X  3) 190,260        447 

For  horizontal  forward  movement  (70  X   0.217   X 

6500) 98,735         232 

288,995         679 
Add  for  metabolism  standing  at  rest 88 

767 

The  requirement  of  767  calories  per  hour  exceeds  that 
needed  by  the  trained  bicycle  rider  who  rides  until  exhausted. 
(Seep.  321.) 

Contrary  to  the  observations  of  the  Zuntz  school,  the 
members  of  the  Pike's  Peak  Expedition  found  no  difference  in 
their  metabolism  on  the  summit  of  Pike's  Peak  from  that  at 
sea-level,  either  during  rest  or  when  taking  exercise  such  as 
walking  at  the  rate  of  one  to  five  miles  per  hour.  These 
results  were  obtained  after  acclimatization,  and  this  may 
account  for  the  difference  from  those  obtained  on  Monte 
Rosa. 

The  ventilation  of  the  lungs  of  Durig  and  Zuntz  while  at 
rest  at  different  altitudes  varied  as  follows: 


Respired  in  Liters  per  Minute. 

Zuntz. 
Actual. 

Zuntz. 

Reduced  to  760  Mm. 

Hg  and  o°  C 

Durig. 

Reduced  to  760  Mm. 

Hg  and  0°  C. 

Sea-level 

Col  d'Olen .... 
Monte  Rosa. .  . 

4.61-5.03 
5.97-6.36 
6.86-8.52 

4-15-4-53 
3.99-4.16 
3-71-4-88 

5.OO-5.63 

3-8I-5-07 

4.05-4.60 

43 2  SCIENCE   OF   NUTRITION 

The  actual  amount  of  inspired  air  appears  to  be  about  the 
same  at  different  altitudes,  an  increased  volume  compensating 
for  increasing  rarefaction  of  the  atmosphere. 

The  atmosphere  in  which  one  lives  is  really  the  air  within 
the  alveoli  (Pfliiger).  Durig  and  Zuntz  have  calculated  the 
pressure  of  oxygen  and  carbon  dioxid  within  their  alveoli  at 
different  levels,  and,  measured  in  terms  of  millimeters  of 
mercury,  have  found  them  to  be  as  follows : 

Pressures  in  Mm.  Hg. 

Zuntz  (of  Berlin).  Durig  (of  Vienna). 

02            COj  O2  COi 

At  home — rest 107          36  109  32 

At  home — ascending  walk 109           ^^  99  37 

On  Monte  Rosa — rest 57           21  53  24 

On  Monte  Rosa — horizontal  walk       60           17  55  21 

On  Monte  Rosa — ascending  walk      63           18  55  24 

It  is  evident  from  a  study  of  the  results  that  muscular 
exercise  in  all  these  localities  produces  an  increase  in  the 
alveolar  tension  of  oxygen  and  a  decrease  in  that  of  car- 
bon dioxid.  This  is  brought  about  by  the  stimulation  of 
respiration. 

It  will  be  interesting  to  examine  the  evidence  of  the  effect 
of  decreasing  oxygen  tension  on  the  capacity  of  the  blood  in  the 
lungs  to  absorb  oxygen.  The  usually  accepted  doctrine  that 
atmospheric  air,  shaken  with  blood,  will  practically  saturate 
the  hemoglobin  present,  rests  upon  Hiifner's  experiments  with 
carefully  prepared  solutions  of  hemoglobin.  Loewy  and 
Zuntz,1  however,  show  that  if  normal  blood  be  used  the  satu- 
ration is  89  per  cent,  at  the  most.  On  the  basis  of  this  newer 
work,  Durig  and  Zuntz2  have  calculated  the  saturation  of  the 
hemoglobin  within  the  blood  at  the  different  altitudes.  At 
Berlin,  oxygen  exerting  alveolar  pressures  of  113  and  103  mm. 
would  saturate  the  blood  in  the  lungs  to  the  extent  of  81.9  and 
80.5  per  cent,  respectively.  On  Monte  Rosa  alveolar  oxygen 
at  pressures  of  57  mm.  (Zuntz)  and  53.2  mm.  (Durig)  would 

1  Loewy  and  Zuntz:   "Archiv  fur  Physiologie,"  1904,  p.  207. 

2  Durig  and  Zuntz:   Loc.  cit.,  p.  442. 


METABOLISM   IN  ANEMIA  433 

respectively  cause  a  saturation  to  the  extent  of  69.5  and  68  per 
cent.  The  lowest  recorded  oxygen  pressure  in  the  alveoli 
was  48.3  mm.  (Durig),  which  corresponded  to  65.9  per  cent,  of 
oxyhemoglobin,  and  was  accompanied  by  severe  headache.  A 
quickened  heart-beat  produced  a  more  rapid  circulation  than 
normal.  The  experimenters  find  no  ground  for  believing  that 
there  was  at  any  time  any  real  oxygen  deficiency  in  any  of  the 
important  tissues  of  the  body.  They  consider  that  their 
gradual  ascent  from  sea-level  prevented  the  usual  disturbances 
of  appetite  and  digestion  which  are  probably  caused  by  anemia 
in  the  abdominal  region  (mountain  sickness). 

Lactic  acid  has  been  found  in  increased  amounts  in  the 
blood  of  individuals  on  high  mountains.1  Acidosis  quickens 
the  respiration  and  lowers  the  carbon  dioxid  content  of  the 
blood  and  raises  the  oxygen  pressure  in  the  lungs  (see  p.  218). 
In  mountain  sickness  the  body  temperature  may  rise  as  high 
as  420  C.,2  a  temperature  which  favors  the  free  dissociation  of 
oxyhemoglobin.3 

Boycott  and  Haldane4  found  in  experiments  on  themselves 
when  they  were  confined  in  a  steel  pneumatic  cabinet  that  if 
the  atmospheric  pressure  was  reduced  to  356  mm.  of  mercury, 
corresponding  to  a  height  of  6000  meters  ( =  20,000  feet)  the 
oxygen  pressure  in  the  alveoli  fejl  to  30  mm.  and  pronounced 
cyanosis  occurred,  accompanied  first  by  loss  of  memory  and 
then  by  unconsciousness.  There  was  only  slight  hyperpnea. 
Greater  attenuation  of  the  atmosphere  on  mountains  and  in 
balloons  may  often  be  tolerated.  This  they  ascribe  to  a 
gradual  production  of  lactic  acid' within  the  organism  which 
renders  the  respiratory  center  especially  sensitive  to  the  stimu- 
lus of  carbon  dioxid.  They  recommend  that  one  frequently 
partake  of  carbohydrates  when  among  the  higher  mountains 
in  order  that  a  maximum  amount  of  carbon  dioxid  be  furnished 
to  the  blood-stream.    The  carbon  dioxid  pressure  in  the  alveoli 

1  Galeotti:   "Arch.  ital.  de  Biologie,"  1Q04,  xli,  80. 

2  Caspari  and  Loewy:   "Biochemische  Zeitschrift,"  1910,  xxvii,  405. 

3  Barcroft  and  King:    "Journal  of  Physiology,"  1909-10,  xxxix,  374. 

4  Boycott  and  Haldane:   Ibid.,  1908,  xxxvii,  355. 

28 


434 


SCIENCE   OF   NUTRITION 


falls  as  an  accompaniment  of  the  rising  acid  content  of  the 
body.  This  changed  condition  of  the  blood  does  not  pass  off 
at  once  on  return  to  a  lower  level.1  The  respiratory  stimulus 
persists  and  the  beneficial  effects  of  descending  are  promptly 
felt.  At  a  given  altitude  on  the  descent  the  alveolar  oxygen 
pressure  will  therefore  probably  be  higher  than  at  the  same 
altitude  on  the  ascent  on  account  of  the  greater  stimulation  of 
the  respiratory  center. 

These  relations  are  shown  in  the  following  table  compiled 
from  Ward's  experiments  on  himself: 


Pressures  in  Mm.  of  Hg. 

Barometer. 

Alveolar  Air. 

CO2. 

Oj. 

Lister  Institute,  London 

Zermatt 

Monte  Rosa 

769 
633 
443 
633 

37-7 
34-2 
28.5 
28.9 

32-5 

109.0 
81.6 

49.8 

Zermatt,  on  return 

Two  hours  after 

91.0 

One  may  compare  the  statement  of  Boycott  and  Haldane 
that  cyanosis  occurred  in  them  when  the  oxygen  pressure  in 
the  alveoli  fell  to  30  mm.  with  the  statement  of  Loewy  and 
Zuntz2  that  when  the  oxygen  pressure  is  31.8  human  blood 
will  absorb  oxygen  so  that  56  per  cent,  of  its  hemoglobin  is 
saturated.  This  agrees  well  with  the  finding  of  Ringer3  in  the 
author's  laboratory  that  dogs  lose  consciousness  when  their 
hemoglobin  becomes  half-saturated  with  carbon  monoxid  gas. 
Ringer's  dogs,  however,  were  not  beyond  the  power  of  resusci- 
tation until  70  per  cent,  of  the  hemoglobin  was  combined  with 
the  poisonous  gas. 

This  observation  is  similar  to  that  of  Bornstein  and  Miiller,4 

1\Vard:    "Journal  of  Physiology,"  1908,  xxxvii,  378. 

2  Loewy  and  Zuntz:    "Archiv  fur  Physiologie,"  1904,  p.  214. 

3  Ringer:    Unpublished. 

4  Bornstein  and  Miiller:   "Archiv  fur  Physiologie,"  1907,  p.  47c. 


METABOLISM   IN   ANEMIA  435 

who  have  shown  that  death  occurs  when  70  per  cent,  of  the 
hemoglobin  of  the  blood  is  converted  into  methemoglobin  by 
magnesium  chlorid.  Rapid  recovery  takes  place  if  the  process 
is  not  carried  so  far  as  this. 

The  discovery  of  Viault1  that  at  an  altitude  of  4000  meters 
the  number  of  red  blood-cells  increased  to  7,000,000  and 
8,000,000  per  cubic  mm.  of  blood  appeared  at  first  to  in- 
dicate a  compensatory  increase  in  oxygen-combining  power 
during  life  in  rarefied  air.  An  increase  in  the  quantity  of 
hemoglobin  has  been  positively  shown  by  Zuntz  and  his  co- 
workers.2 

While  in  the  high  altitudes  of  Monte  Rosa,  von  Wendt3 
noticed  a  retention  of  nitrogen,  iron,  and  potassium  which  he 
suggests  was  in  part  used  for  the  construction  of  new  red 
blood-corpuscles,  in  part  for  the  upbuilding  of  new  muscu- 
lature. 

The  Pike's  Peak  Expedition  already  referred  to  does  not 
fully  agree  with  the  interpretations  of  the  Zuntz  school.  The 
numerous  visitors  who  reached  the  summit  of  Pike's  Peak  by 
train  and  remained  only  about  three-quarters  of  an  hour 
showed  blueness  of  the  lips  and  cheeks,  accompanied  by  great 
hyperpnea  on  exertion.  Only  a  few  became  miserable  and 
faint  and  required  oxygen  for  their  restoration.  Among  those 
who  arrived  on  foot,  frequently  after  ten  hours  of  effort,  the 
symptoms  were  much  more  severe :  nausea,  vomiting,  headache, 
and  fainting  being  common.  The  nose-bleed  traditionally 
assigned  as  characteristic  of  life  in  rarefied  atmospheres  is 
mythical.     The  process  of  acclimatization  follows  these  lines: 

(1)  The  production  of  acids  which  reduce  the  alkalinity  of  the 
blood,  this  in  turn  stimulating  the  respiratory  center  with  a 
resultant  increase  in  ventilation  of  the  lungs,  a  fall  in  the  alveo- 
lar carbon  dioxid  tension  and  an  increase  in  the  oxygen  tension ; 

(2)  an  increase  up  to  150  per  cent,  of  the  normal  amount  of 

1  Viault:    "Comptes  rendus  de  I'academie  des  sciences,"  1890,  cxi,  917. 

2  Zuntz,  Loewy,  Miiller,  and  Caspari:  "Hohenklima  und  Bergwanderungen 
in  ihrer  Wirkung  auf  den  Menschen,"  Berlin,  1906. 

3  von  Wendt:   "Skan.  Archiv  fur  Physiologie,"  1911,  xxiv,  247. 


436  SCIENCE   OF   NUTRITION 

hemoglobin.  These  factors  are  of  such  influence  that  even 
more  than  the  normal  quantity  of  oxygen  may  be  carried  to 
the  tissues.  The  hemoglobin  was  found  to  be  saturated  with 
oxygen  to  an  extent  of  95  per  cent.,  which  is  contrary  to  the 
teachings  of  Zuntz.  The  authors  believe  that  only  adherence 
to  the  theory  that  the  alveolar  epithelium  secretes  oxygen 
from  the  air  into  the  blood  will  explain  this  phenomenon.  The 
pulse  and  blood-pressure  were  but  little  affected.  On  passing 
from  the  summit  of  the  mountain  to  the  sea-level  a  fortnight 
is  required  before  the  stimulus  to  the  respiratory  center 
disappears  and  the  alveolar  carbon  dioxid  tension  becomes 
normal,  and  several  weeks  pass  before  the  total  quantity  of 
hemoglobin  in  the  body  returns  to  the  normal.  It  is  evident 
that  in  unacclimated  persons  balloon  ascents  and  the  like 
are  to  a  greater  extent  dangerous  to  life  than  in  those  who  have 
undergone  climatic  adaptation  to  high  altitudes.  Into  all 
phases  of  the  fascinating  work  of  the  Pike's  Peak  Expedition 
it  is  impossible  to  go. 

The  work  was  ably  supplemented  by  that  of  Miss  Fitz- 
gerald,1 who  worked  among  acclimated  mine  attendants  and 
their  wives,  persons  who  had  lived  a  year  or  more  at  different 
heights  above  the  sea-level  in  Colorado,  some  of  them  having 
been  born  in  these  localities.  The  records  included,  among 
others,  some  made  at  Denver  (5100  ft.),  Colorado  Springs 
(6000  ft.),  Cripple  Creek  (10,000  ft.),  Camp  Bird  Mine 
(11,300  ft.),  Lewis  (12,500  ft.),  and  Pike's  Peak  (14,100  ft.). 
Miss  Fitzgerald  showed  that  for  every  100  mm.  fall  in  baro- 
metric pressure  there  was  an  increase  of  10  per  cent,  above  the 
amount  of  hemoglobin  present  in  the  body  at  the  level  of  the 
sea,  the  law  holding  true  for  both  sexes.  Also,  for  every  fall 
of  100  mm.  in  the  atmospheric  pressure  there  is  a  fall  of  4.2 
mm.  in  the  pressure  of  alveolar  carbon  dioxid,  accompanied  by 
a  progressive  fall  in  the  oxygen  pressure. 

From  the  facts  she  makes  the  following  computation: 

1  Fitzgerald:  "Transactions  of  the  Royal  Society  of  London,"  1913,  Series 
B,  cciii,  351. 


METABOLISM   IN   ANEMIA 


437 


TABLE  SHOWING  THE  TENSION  OF  THE  ALVEOLAR  GASES  IN 
ACCLIMATED   INDIVIDUALS 


Approximate  Altitude  When 

Alveolar  Air. 

Atmospheric 
Pressure. 

Column  =  15°  C. 

Percentage. 

Partial  I 

'ressure. 

Feet. 

Meters. 

O2. 

CO2. 

O2. 

CO2. 

Mm. 

Mm. 

Mm. 

Sea-level. 

Sea-level. 

760 

14-33 

5-58 

I02.2 

39-8 

122 

400 

75° 

14.26 

5-59 

IOO.O 

39-2 

698 

2,2QO 

700 

14.17 

6.66 

92.9 

37-i 

1326 

4,35° 

650 

14.01 

5.80 

84-5 

35-o 

2004 

6,^78 

600 

I3-83 

5-95 

76.5 

32-9 

2743 

8,999 

55° 

13.62 

6.12 

68.5 

30.8 

3552 

",653 

500 

I3-36 

6-34 

60.5 

28.7 

4447 

14,589 

45° 

13-05 

6.60 

52.6 

26.6 

5445 

17,864 

400 

12.64 

6-94 

44.6 

24-5 

6579 

21,584 

350 

12.10 

7-39 

36.7 

22.4 

7889 

25,882 

300 

n-34 

8.02 

28.7 

20.3 

9437 

30,960 

250 

10.24 

8-97 

20.8 

18.2 

Each  successive  diminution  of  ioo  c.c.  of  barometric 
pressure  causes  a  greater  absolute  increase  in  the  ventilation 
of  the  lung  and  this  introduces  more  oxygen.  The  full  re- 
action, however,  is  not  effected  in  short  periods.  Thus,  in  the 
experiment  by  Boycott  and  Haldane  (see  p.  433)  in  which  they 
subjected  themselves  to  a  barometric  pressure  of  350  mm., 
their  alveolar  carbon  dioxid  tensions  were  31.2  and  27.3 
mm.  respectively.  In  an  acclimatized  individual  the  carbon 
dioxid  tension  at  this  level  of  the  barometer  would  have 
been  22.4  mm.  and  he  would  have  had  3.2  per  cent,  more 
oxygen  in  his  alveoli  than  Haldane  had.  Acclimatization 
involving  this  reaction,  as  well  as  increasing  the  quantity  of 
hemoglobin,  would  have  prevented  the  cyanosis  and  uncon- 
sciousness which  followed  in  the  experiments  of  Boycott  and 
Haldane  when  they  were  in  the  respiration  chamber. 

Durig  and  Zuntz1  made  a  voyage  to  Teneriffe,  one  of  the 
Canary  Islands  (situated  at  about  the  latitude  of  Florida), 
and  there  ascended  a  volcano  which  rises  to  a  height  of  3160 

1  Durig  and  Zuntz:   "Biochemische  Zeitschrift,"  1912,  xxxix,  435. 


438  SCIENCE   OF  NUTRITION 

meters.  They  found  no  essential  difference  in  their  metab- 
olism from  that  at  Col  d'Olen  (2865  meters)  except  a  slight 
increase  due  to  a  quickened  rate  of  respiration  which  they 
ascribed  to  the  effect  of  sunlight. 

The  results  of  these  varied  experiments  confirm  the  inde- 
pendence of  the  metabolism  of  variations  in  atmospheric  pres- 
sure as  regards  all  the  customary  habitats  of  mankind.  The 
beneficial  properties  of  mountain  air  may  be  largely  the  same 
as  those  derived  at  watering-places,  i.  e.,  outdoor  life,  cool  air, 
exercise,  diversion  through  change  of  scene,  mental  rest,  and, 
finally,  suggestion  of  benefits  received.  The  dry,  crisp  air 
undoubtedly  benefits  catarrhal  disturbances,  which  are,  on 
the  other  hand,  aggravated  by  the  climate  of  the  sea-shore. 

In  the  search  for  conditions  which  might  reduce  the  inten- 
sity of  metabolism,  the  influence  of  the  internal  secretions  of 
the  sexual  glands  has  been  prominently  considered.  Careful 
experiments  of  Liithje,1  however,  show  that  castration  in  dogs 
of  both  sexes  has  no  influence  on  the  metabolism.  It  is  said, 
however,  that  removal  of  the  ovaries  reduces  for  a  time  the 
number  of  red  blood-corpuscles,  and  it  is  suggested  that  ova- 
rian insufficiency  may  be  the  cause  of  chlorosis.2 

Grafe3  has  analyzed  29  cases  of  stupor,  and  in  the  majority 
of  individuals  has  found  no  variation  from  the  usual  normal 
metabolism.  In  8  cases,  however,  there  was  a  metabolism 
which  was  between  17  and  39  per  cent,  lower  than  normal. 

It  has  already  been  stated  that  Means,  using  the  new 
Du  Bois  formula  for  surface  area,  could  find  no  departure 
from  the  normal  metabolism  in  simple  obesity. 

Means4  finds  a  diminished  metabolism  in  hypopituitarism 
with  accompanying  obesity.  This  condition  of  dystrophia 
adipo  so  genitalis  is  stated  by  Cushing5  to  show  an  abnormally 

1  Liithje:   "Archiv  fiir  exp.  Path,  und  Pharm.,"  1902,  xlviii,  184. 

2  Breuer  and  v.  Seiller:   Ibid.,  1903,  1,  169. 

3  Grafe:    "Deutsches  Archiv  fiir  klin.  Med.,"  1911,  cii,  15. 

4  Means:   "Journal  of  Medical  Research,"  1915,  xxxii,  121. 
6  Cushing:   "The  Pituitary  Body  and  Its  Disorders,"  1912. 


METABOLISM   IN   ANEMIA  439 

high  tolerance  for  carbohydrate,  whereas  in  acromegaly  the 
tolerance  is  decreased.  In  acromegaly  the  basal  metabolism 
is  increased.1 

Forschbach  and  Severin2  (Minkowski's  clinic)  do  not 
agree  with  Cushing,  and  conclude  that  in  the  most  varied 
affections  of  the  hypophysis  (acromegaly,  dystrophia  adiposo- 
genitalis,  hypophyseal  tumors)  there  is  always  hypoglycemia 
and  increased  carbohydrate  tolerance.3  This  is  illustrative  of 
the  disagreement  among  the  best  authorities  upon  the  influence 
of  the  internal  secretions. 

Cushing  and  Goetsch4  and,  before  them,  Gemelli,5  have 
noticed  that  in  hibernating  animals  the  pituitary  gland  not 
only  diminishes  in  size,  but  that  the  cells  of  the  pars  anterior 
completely  lose  their  characteristic  staining  reactions. 

The  literature  regarding  the  action  of  the  internal  secre- 
tions upon  metabolism  is  very  large.  Much  of  it  is  crudely 
unscientific.  Where  several  unknown  factors  are  interacting, 
as  happens  in  this  field  of  study,  it  is  pleasant  to  give  the 
fancy  full  play,  and  this  is  also  a  perfectly  harmless  occupation 
provided  such  mental  activity  does  not  develop  into  hallucina- 
tion. Du  Bois.  in  writing  concerning  exophthalmic  goiter, 
makes  the  ironical  proposal,  "For  the  purpose  of  simplicity 
in  this  paper  one  may  consider  the  symptoms  of  exoph- 
thalmic goiter  to  be  caused  by  hypersecretion  of  the  thy- 
roid, and  allow  the  reader  to  select  for  himself  those  cases 
in  which  he  believes  other  glands  to  be  involved." 

The  thyroid  gland  is  a  gland  whose  internal  secretion 
profoundly  affects  the  amount  of  general  metabolism.  No 
other  gland  compares  with  it  in  this  regard.  This  influence  is 
apparently  brought  about  by  a  substance  called  thyroiodin, 

1  Magnus-Levy:  "Zeitschrift  fur  klinische  Medizin.,"  1906,  Lx,  179. 

2  Forschbach  and  Severin:  "Archiv  fur  exp.  Path,  und  Pharm.,"  1914,  lxxv, 
168. 

3  For  a  good  review  of  the  literature  read  Simpson,  S.:  "American  Medi- 
cine," 1914,  ix,  219. 

4  Cushing  and  Goetsch:    "Journal  of  Experimental  Medicine,"  1915,  xxii, 

6  Gemelli:    "Archives  pour  la  science  medicale,"  1905,  xxx,  341. 


440  SCIENCE   OF   NUTRITION 

which,  when  produced  in  normal  quantities,  maintains  the 
proper  functions  of  the  nervous  system.  A  subnormal  pro- 
duction reduces  the  activity  of  the  nervous  system  and  in- 
cidentally the  quantity  of  metabolism.  An  overproduction 
increases  the  irritability  of  the  nervous  apparatus  and  raises 
the  metabolism.  Myxedema  is  a  condition  in  which  the  thy- 
roid gland  has  atrophied  and  its  secretion  is  no  longer  available. 
Exophthalmic  goiter  presents  the  opposite  phase,  since  here  a 
superabundance  of  thyroidin  is  believed  to  be  produced. 
Symptoms  somewhat  akin  to  the  latter  condition  may  be 
induced  in  normal  animals  and  man  by  ingesting  thyroid 
extracts. 

Magnus-Levy1  found  the  carbon  dioxid  output  increased 
after  giving  a  normal  man  thyroid  extracts.  Fritz  Voit2  finds 
the  same  to  be  true  of  a  dog,  and  also  that  more  protein  is 
metabolized.  It  is  this  latter  action  which  contraindicates 
thyroid  feeding  in  obesity.  However,  Rheinboldt3  states  that 
a  man  fed  with  thyroid  extracts  may  be  maintained  in  nitrogen 
equilibrium  if  much  protein  be  allowed  in  the  diet. 

That  the  thyroid  has  a  profound  effect  upon  the  endogenous 
protein  metabolism  is  evidenced  by  the  fact  that  after  its 
removal  in  the  dog  the  usual  increases  in  protein  metabolism 
which  follow  the  administration  of  phlorhizin4  (see  p.  460)  or 
which  follow  partial  asphyxia5  do  not  occur. 

Andersson  and  Bergman6  have  given  large  quantities  of  thy- 
roid extract  to  a  man  who  was  kept  in  perfect  quiet,  and  no 
increased  output  of  carbonic  acid  was  noticed.  They  attribute 
the  increased  metabolism  which  is  usually  observed  to  the 
increased  muscle  tonus  caused  by  the  highly  irritated  central 
nervous  system.     A  high  metabolism  is  observed  in  cases  of 

1  Magnus-Levy:   "Berliner  klinische  Wochenschrift,"  1895,  xxxii,  650. 

2  Voit,  F.:   "Zeitschrift  fur  Biologie,"  1897,  xxxv,  116. 

3  Rheinboldt:   "Zeitschrift  fur  klin.  Med.,"  1906,  lviii,  425. 

4Lusk:  "Proceedings  of  the  International  Congress  of  Medicine,"  1913, 
Sec.  II,  Pt.  2,  p.  13. 

BMansfeld:   "Pfliiger's  Archiv,"  1915,  clxi,  502. 

6  Andersson  and  Bergman:  "Skan.  Archiv  fur  Physiologie,"  1898,  viii, 
326. 


METABOLISM   IN   ANEMIA 


44I 


exophthalmic  goiter.  Freidrich  Muller1  reports  a  case  of  an 
individual  weighing  only  29  kilograms  who  constantly  lost 
weight  notwithstanding  a  daily  diet  containing  68  grams  of 
protein  with  58  calories  per  kilogram.  Under  such  circum- 
stances there  is  undoubtedly  an  abnormally  high  destruction  of 
both  protein  and  fat.  The  increased  protein  destruction  has 
been  attributed  to  toxic  influence  of  the  thyroid  secretion. 
Magnus-Levy2  finds  an  increased  oxygen  intake  in  cases  of 
exophthalmic  goiter  amounting  to  22,  42,  and  70  per  cent, 
above  the  normal. 

Steyrer3  made  interesting  experiments  on  the  metabolism 
in  this  disease.  The  patient  was  twenty-one  years  old, 
temperature  normal;  the  total  metabolism  during  two  days 
was  determined  twice  at  intervals  one  month  apart  and  while 
the  person  was  resting  in  bed.  During  the  second  period  the 
disease  had  made  considerable  progress,  the  patient  having  a 
hot  skin  and  being  in  a  highly  nervous  state. 


Day. 

Calories  of 
Metabolism. 

Weight 
in  Kg. 

Calories 
per  Kg. 

Period  I 

Period  II  Cone  month  later) 

2665 

2731 

3666 

.   33i8 

45-1 
46.4 
48.2 

47-5 

59-1 
58.9 
76.I 
69.9 

Calorimetric  studies  upon  12  thyroid  cases  have  been 
made  by  Du  Bois4  and  the  literature  has  been  very  fully  con- 
sidered by  him.  The  accompanying  table  epitomizes  the 
results  obtained  by  Du  Bois  with  3  cases  of  exophthalmic 
goiter  and  with  1  cretin  thirty-six  years  of  age. 


1  Muller:    "Deutsches  Archiv  fur  klin.  Medizin,"  1893,  li,  361. 

2  Magnus-Levy:     von  Noorden's  "Handbuch  der  Pathologie  des  Stoff- 
wechsels,"  1907,  II,  p.  325. 

a  Steyrer:   "Zeitschrift  f.  exp.  Path,  und  Therapie,"  1907,  iv,  720. 
4  Du  Bois:   "Archives  of  Internal  Medicine,"  1916,  xvii,  915. 


442 


SCIENCE   OF   NUTRITION 


THE    METABOLISM     OF    3     PATIENTS     WITH    EXOPHTHALMIC 
GOITER   AND   OF    1    CRETIN 


Subject  and 
Date. 


Case  I: 

Feb.   16,  1914. 

20,  1914. 

21,  1914. 
25,  1914. 
24,  1914. 
23,  IQI5- 


Feb. 
Feb. 
Feb. 
April 
April 


Case  II: 

March  22,  1915. 
May     11,  1915. 


Case  III: 
March  12,  1915. 

Case  XII 
(Cretin): 

April     10,  1914. 

April     14,  1914. 

April     21,  1914. 

April     23,  1914. 

May       1,  1914. 


Character  of 
Experiment. 


Pulse- 
rate. 


Basal 

Basal 

Glucose,  100  gm. .  . . 
Casein,  N  =  8.9  gm. 

Basal 

Basal,  one  year  later 

Basal 

Basal  two  weeks 
after  ligating  arte- 
ries   

Basal 

Basal 

Glucose,  100  gm 

Casein,  N  =  3.6  gm. 

Basal 

After  thyroid  extract 


137 
in 
i°5 
138 
120 

go 


107 
134 


Calories 
per  Sq. 
Meter, 
Du  Bois 
Formula. 


69.4 
63-7 
68.8 
71.9 
60.9 
57-7 


33° 
37-9 
34-9 
31.0 
39-8 


Per  Cent. 

Per  Cent. 

Rise  Above 

Rise  Above 

Normal 

Patient's 

Basal  or 

Own 

39.7  Cal. 

Basal. 

4  7S 

+  60 

+  9 

+  14 

+  S3 

+  45 

+  50 

+  79 

+  87 

-17 

+  15 

+  13 

—  22 

+  0 

+  28 

R.  Q. 


0.76 
0.77 
0.94 
0.83 
0.78 
0.77 


0.79 
0.76 
0.78 


0.92 
1. 00 
0.93 
0.87 
0.79 


The  total  difference  between  direct  and  indirect  calorimetry 
in  the  12  cases  was  2.9  per  cent. 

The  specific  dynamic  action  of  protein  and  glucose  was 
within  the  normal  limits,  and  glucose  was  oxidized  in  an  en- 
tirely normal  fashion,  even  in  the  presence  of  some  glycosuria. 
In  one  experiment  (Case  I)  89  per  cent,  of  his  energy  produc- 
tion was  derived  from  glucose. 

Forschbach  and  Severin,1  in  Minkowski's  clinic,  state  that 
the  administration  of  100  grams  of  glucose  in  exophthalmic 
goiter  does  not  invariably  produce  glycosuria.  The  glycosuria 
is  probably  to  be  explained  by  a  difficulty  of  glycogen  reten- 
tion in  hyperthyroidism.  When  thyroid  extracts  are  given  to 
rabbits  or  to  dogs  the  liver  contains  much  less  glycogen  than 
normally.2 

1  Forschbach  and  Severin:  "Archiv  fur  exp.  Path,  und  Pharm.,"  1914,  lxxv, 
168. 

2  Parhon:  "Journal  de  Physiologie  et  de  Pathologie  gen£rale,"  1913,  xv,  75; 
Cramer  and  Krause:  "Proceedings  of  the  Royal  Society,"  1913,  Series  B, 
lxxxvi,  550. 


METABOLISM   IN   ANEMIA  443 

This  inability  to  store  the  normal  amount  of  glycogen  is 
the  probable  explanation  of  the  fact  that  the  respiratory  quo- 
tients found  during  the  determinations  of  the  basal  metab- 
olisms of  patients  with  hyperthyroidism  invariably  show  a 
lower  average  level  than  the  normal. 

Du  Bois  finds  that  the  height  of  the  metabolism  gives  the 
best  index  of  the  severity  of  the  disease  and  classifies  very 
severe  cases  as  showing  an  increase  of  75  per  cent,  above  the 
normal  heat  production,  severe  cases  as  showing  over  50  per 
cent.,  and  moderately  severe  and  mild  cases  as  showing  less 
than  50  per  cent,  increase  above  the  normal  basal  metabolism. 
Rest  of  a  week  in  bed  usually  caused  a  10  per  cent,  fall  in 
metabolism.  Thyroid  sera,  ergotin,  and  quinin  hydrobromate 
had  little  effect.  Ligation  of  the  thyroid  arteries  was  fol- 
lowed by  a  rise  in  metabolism  in  most  cases.  There  was  no 
indication  that  any  conservative  form  of  treatment  was  more 
effective  than  mental  and  physical  rest. 

In  myxedema  the  metabolism  is  reduced  and  there  is  a  fall 
in  body  temperature.  Anderson1  reports  a  case  of  a  woman 
whose  metabolism  was  as.  low  as  1260  calories  or  18.8  per 
kilogram:  after  treatment  for  nine  months  with  thyroid 
extracts  the  heat  production  rose  to  2099  calories,  or  32.3  per 
kilogram.  These  latter  are  normal  values.  The  tempera- 
ture rose  to  normal  with  the  increase  in  metabolism. 

The  cretin  investigated  by  Du  Bois  (see  table  on  p.  442) 
had  a  basal  metabolism  which  was  20  per  cent,  less  than  the 
normal  adult.  Response  to  the  specific  dynamic  action  of 
food  was  normal.  The  individual,  by  Binet's  tests,  had  the 
mentality  of  a  child  of  seven  years,  though  his  age  was  thirty- 
six.  This  condition  is  a  rare  example  in  which  the  metabolic 
processes  are  permanently  depressed. 

With  the  possession  of  such  a  gland  as  the  thyroid,  whose 
suppression  may  diminish  metabolism  20  per  cent,  and  whose 
stimulation  may  increase  it  100  per  cent.,  it  is  truly  strange 

1  Anderson:  "Hygeia,"  Stockholm,  1898  (quoted  in  Tigerstedt's  "Lehrbuch 
der  Physiologie"). 


444  SCIENCE    OF   NUTRITION 

that  a  normal  person  should  have  a  basal  metabolism  so 
regulated  as  to  correspond  to  a  definite  heat  loss  per  square 
meter  of  body  surface.  It  is  no  wonder  that  the  law  of  surface 
area  should  be  assailed  as  incredible  and  irrational.  The  real 
wonder  is  that  the  law  is  true. 

Of  late  years  there  has  been  a  sharp  differentiation  be- 
tween the  functions  of  the  thyroid  and  those  of  the  parathy- 
roid glands.  Clonic  convulsions  are  a  symptom  following  para- 
thyroidectomy, and  during  these  periods  the  temperature  rises. 
MacCallum1  reports  that  the  temperature  of  a  dog,  in  which 
after  parathyroidectomy  violent  tetany  developed,  rose  from 
390  to  43.20  during  the  attack.  The  administration  of  calcium 
acetate  stopped  the  convulsions  in  a  few  minutes  and  within 
half  an  hour  the  temperature  fell  to  38. 90. 

Wilson,  Stearns,  and  Thurlow2  report  that  after  para- 
thyroidectomy a  condition  of  alkalosis  develops  in  the  blood 
which  is  neutralized  by  the  production  of  acids  incident  to 
tetany,  or  the  tetany  may  be  prevented  by  intravenous  in- 
jection of  j  hydrochloric  acid.  The  action  of  calcium  salts 
is  to  lower  the  dissociation  constant  of  hemoglobin  and  the 
alveolar  tension  of  carbon  dioxid,  effects  which  are  also  brought 
about  by  acids.  Underhill3  states  that  neither  thyroidectomy 
nor  the  simultaneous  removal  of  two  parathyroids  out  of  four 
will  alter  the  utilization  of  glucose  by  dogs.  Only  after  the 
removal  of  three  parathyroids  is  the  assimilation  limit  for  glu- 
cose reduced. 

1  MacCallum:  "Fever,"  Harvey  Society  Lecture,  "Archives  of  Internal 
Medicine,"  1908,  ii,  572. 

2  Wilson,  Stearns,  and  Thurlow:  "Journal  of  Biological  Chemistry,"  1915, 
xxiii,  89. 

3  Underhill  and  Hilditch:  "American  Journal  of  Physiology,"  1909-10, 
xxv,  66;  Underhill  and  Blatherwick:  "Journal  of  Biological  Chemistry,"  1914. 
xviii,  87. 


CHAPTER  XVI 

METABOLISM  IN  DIABETES  AND  IN  PHOSPHORUS- 
POISONING 

It  is  said  that  the  sweet  taste  of  diabetic  urine  was  familiar 
to  Susruta,  a  physician  who  lived  in  India  during  the  seventh 
century.  The  disease,  then  as  now,  may  have  been  more 
prevalent  among  the  Hindoos  than  elsewhere  in  the  world. 
In  Europe  the  sweet  taste  of  diabetic  urine  was  discovered  by 
Thomas  Willis  in  1674,  but  it  was  not  till  after  another  hundred 
years  that  Dobson,  in  17 15,  showed  that  the  taste  was  due  to 
the  presence  of  sugar.  Subsequently  the  coexistence  of  a 
hyperglycemia  was  established. 

Claude  Bernard  found  that  the  stimulation  by  puncture  of 
a  group  of  cells  (the  "diabetic  center")  lying  in  the  medulla 
near  the  floor  of  the  fourth  ventricle  gave  rise  to  an  excretion 
of  sugar  in  the  urine.  This  experiment  is  the  source  of  the 
false  impression  that  diabetes  is  essentially  of  nervous  origin. 
It  is  called  la  piqure. 

Diabetes1  is  a  disease  of  particular  interest,  since  it  is  a 
departure  from  the  physiologic  condition  involving  the  capac- 
ity of  the  organism  to  care  for  sugar  in  the  normal  fashion. 
All  the  symptoms  are  due  to  this  one  fact.  No  other  disease 
has  been  more  thoroughly  investigated.  The  study  of  diabetes 
has  wonderfully  developed  a  knowledge  of  the  intermediary 
metabolism  of  protein,  fat,  and  carbohydrates.  In  presenting 
the  details  to  the  reader  it  may  be  remarked  that  the  work 
done  is  prophetic  of  possible  accomplishment  along  scientific 
lines  in  the  study  of  disease.  It  is  typical  of  that  "scientific 
medicine"  which  affrights  the  spirits  devoted  to  a  passing 
empiricism. 

1  For  an  excellent  monograph  on  this  subject  consult  Foster,  "Diabetes 
Mellitus,"  1915. 

445 


446  SCIENCE    OF   NUTRITION 

The  foundation  of  modern  knowledge  on  this  subject  was 
laid  by  von  Mering  and  Minkowski1  and  by  Minkowski2  work- 
ing alone,  who  extirpated  the  pancreas  in  dogs  and  demon- 
strated that  such  animals  became  diabetic. 

Peligot3  long  ago  showed  that  the  sugar  in  diabetic  urine 
was  glucose.  Geelmuyden4  analyzed  more  than  30  diabetic 
urines  which  contained  much  sugar  and  could  not  detect  the 
presence  of  maltose  or  any  of  the  known  disaccharids, 
though  he  suspected  the  presence  of  monosaccharids  other 
than  glucose.  Von  Noorden5  states  that  fructose  appears  in 
the  urine  in  cases  of  severe  diabetes. 

The  causes  of  the  appearance  of  sugar  in  the  urine  are: 
(1)  Either  the  organism  cannot  burn  sugar,  which  therefore 
accumulates  in  the  blood  in  excess  of  the  normal,  and  is  filtered 
through  the  kidney  (diabetes  mellitus,  experimental  pancreas 
diabetes);  or  (2)  some  tissues  may  lose  their  sugar-retaining 
function  so  that  the  normal  regulatory  control  of  the  quantity 
of  blood-sugar  is  lost  or  diminished  (Bernard's  piqure,  ali- 
mentary glycosuria,  phlorhizin  glycosuria). 

The  stimulation  of  Bernard's  "diabetic  center"  is  effective 
in  its  results  only  when  the  liver  contains  glycogen.6  This 
form  of  glycosuria  cannot  be  obtained  in  a  starving  animal.  It 
is  attributed  to  a  sudden  flushing  of  the  liver  with  blood  and  a 
conversion  of  glycogen  into  sugar,  so  that  hyperglycemia  and 
sugar  elimination  through  the  kidney  follow. 

Ishimori,7  working  under  Hofmeister's  direction,  concluded 
that  although  in  the  fasting  rabbit  glycogen  disappeared  in 
the  liver  from  the  periphery  of  the  lobule  toward  the  center 
without  evidence  of  glycogen  as  such  appearing  to  be  dis- 
charged, in  the  case  of  piqure,  glycogen  itself  passed  from  all 

1  von  Mering  and  Minkowski:  "Archiv  fur  exp.  Path,  und  Pharm.,"  1890, 
xxvi,  371. 

2  Minkowski:   Ibid.,  1893,  xxxi,  85. 

3  Peligot:  "Compt.  rend,  de  l'Acad.  des  Sciences,"  1838,  vii,  106. 

4  Geelmuyden:   "Zeitschrift  fur  klinische  Medizin,"  1910,  lxx,  287. 
6  von  Noorden:   "Diabetes,"  1905,  p.  50. 

6  Dock:   "Pfluger's  Archiv,"  1872,  v,  571. 

7  Ishimori:   "Biochemische  Zeitschrift,"  1912-13,  xlviii,  332. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING     447 

the  cells  into  the  surrounding  lymph-spaces  and  dilated  blood- 
vessels. It  has  been  suggested  that  piqure  acts  through  a 
stimulation  of  the  adrenal  secretion,  but  Freund  and  Marchand1 
find  after  the  extirpation  of  the  adrenals  that  piqure  causes 
hyperglycemia,  and  argue  that  the  adrenals  are  not  the  cause. 

Hofmeister2  has  discovered  that  the  fasting  organism  is 
more  susceptible  to  alimentary  glycosuria  than  the  well-fed 
one.  He  calls  such  a  condition  "starvation  diabetes"  (see 
below) . 

Asphyxial  glycosuria,  discovered  by  Araki,  has  already  been 
described  (see  p.  422).  Macleod3  found  that  if  the  liver  were  ex- 
cluded from  the  circulation  by  means  of  an  Eck  fistula  in  the  dog 
no  hyperglycemia  followed  asphyxiation.  Furthermore,  sever- 
ance of  the  hepatic  nerves  did  not  prevent  asphyxial  hyper- 
glycemia. Macleod  therefore  concluded  that  acids  carried 
in  asphyxial  blood  produced  glycogenolysis  in  the  liver  cells. 
Analogous  results  were  obtained  by  Blum,4  who  found  that 
strychnin  convulsions  freed  a  dog's  liver  of  its  glycogen  even 
after  cutting  the  vagus  and  splanchnic  nerves.  He  concluded 
that  chemical  co-ordination  was  established  through  the  blood 
between  the  muscle  cells  in  need  of  sugar  and  the  liver  which 
could  supply  it. 

Elias5  found  that  the  intravenous  injection  of  acids  into 
dogs  resulted  in  a  discharge  of  glycogen  by  the  liver  in 
hyperglycemia  and  in  glycosuria.  He  suggested  that  the 
acidosis  in  diabetes  mellitus  might  exert  a  similar  influence. 
In  a  later  paper  Elias  and  Kolb6  state  that  the  hunger  diabetes 
of  Hofmeister  is  due  to  the  reduced  alkalinity  of  the  blood 
which  accompanies  fasting.  Administration  of  alkali  reduced 
or  prevented  this  form  of  glycosuria.  Hence,  acidosis  prevents 
the  normal  storage  of  glycogen. 

1  Freund  and  Marchand:  "Archiv  fur  exp.  Path,  und  Pharm.,"  19 14,  lxxvi, 

324- 

2  Hofmeister:   Ibid.,  1890,  xxvi,  355. 

3  Macleod:   "American  Journal  of  Physiology,"  1908-09,  xxiii,  278. 

4  Blum,  P.:    "Pfliiger's  Archiv,"  1915,  clxi,  516. 

5  Elias:  "Biochemische  Zeitschrift,"  1912-13,  xlviii,  120. 

6  Elias  and  Kolb:  Ibid.,  1913,  lii,  331. 


448  SCIENCE    OF   NUTRITION 

The  acidosis  which  rapidly  develops  in  both  pancreas 
and  phlorhizin  glycosuria  is,  therefore,  the  cause  of  the  almost 
complete  removal  of  glycogen  from  the  liver. 

Minkowski1  noted  that  the  livers  of  his  depancreatized 
dogs  were  free  from  glycogen,  and  this  fact  has  been  confirmed 
by  other  observers.  He  also  found  that  when  fructose  was 
given  glycogen  could  be  stored. 

Verzar2  has  reported  that  the  dog  does  not  completely 
lose  its  power  to  oxidize  glucose  until  the  fourth  day  after 
pancreatectomy.  Intravenous  injection  of  a  10  per  cent, 
glucose  solution  sufficient  in  quantity  to  raise  the  blood-sugar 
from  0.3  to  0.9  per  cent,  did  not  thereafter  affect  the  respiratory 
quotient.  During  the  first  seven  days,  however,  injection  of 
fructose  was  able  to  raise  the  respiratory  quotient,  though  on 
the  twelfth  and  twenty-first  days  the  administration  of 
fructose  was  also  without  effect  on  this  quotient.  One  may 
interpret  the  work  as  indicating  that  on  the  fourth  day  the 
organism  lost  the  power  to  split  glucose,  whereas  the  ability 
to  break  fructose  into  oxidizable  trioses  or  methyl-glyoxal 
remained  intact.  Later,  the  power  to  oxidize  the  three  carbon 
atom  chains  was  also  lost,  though  the  power  to  produce  them 
and  reconstruct  them  into  glucose  was  preserved.  There  is 
no  evidence  existing  which  proves  that  sugar  in  order  to  be 
oxidized  must  first  be  converted  into  glycogen.  That  the 
diabetic  liver  cannot  form  glycogen  from  glucose  appears 
from  the  experiments  of  Epstein  and  Baehr,3  who  performed 
pancreatectomy  and  double  nephrectomy  upon  a  cat  which  had 
fasted  nine  days.  The  blood-sugar,  which  before  the  operation 
had  been  0.06  per  cent.,  rose  to  1.1  percent,  forty-eight  hours 
after  the  operation,  at  which  time  the  animal  was  killed. 
The  liver  proved  to  be  free  of  glycogen  and  the  muscle  con- 
tained only  0.06  per  cent,  of  the  substance. 

Glycosuria  which  follows  exposure  to  cold,  as  originally 

1  Minkowski:   Loc.  cit. 

2  Verzar:   "Biochemische  Zeitschrift,"  1014,  lxvi,  75. 

3  Epstein  and  Baehr:   "Journal  of  Biological  Chemistry,"  1916,  xxiv,  1. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING     449 

observed  by  Araki,1  is  very  likely  due  to  the  asphyxial  element 
brought  about  by  vasoconstriction. 

Bohm  and  Hoffmann2  report  that  a  dog  barking  at  a  cat 
induces  glycosuria  in  the  cat.  Cannon  and  de  la  Paz3  term 
this  "emotional  glycosuria,"  and  have  found  that  the  cat's 
blood  contains  an  increased  quantity  of  epinephrin  as  a 
sequence  to  the  fright.  This  increased  amount  of  epinephrin 
becomes  the  exciting  cause  of  dilatation  of  the  pupil,  inhibition 
of  the  movements  of  stomach  and  intestines,  acceleration  of 
the  heart,  erection  of  the  hairs  on  the  back  and  on  the  tail, 
and  the  discharge  of  glycogen. 

Cannon  has  elaborated  these  results  and  presented  them 
in  the  form  of  a  popular  book  which  holds  that  emotional 
impulses  act  upon  the  adrenals,  causing  them  to  discharge 
epinephrin,  which,  in  turn,  mobilizes  the  physical  and  chemical 
resources  of  the  body  for  supreme  mechanical  effort  in  both  at- 
tack and  defense. 

Tying  down  a  frightened  rabbit  to  a  board  results  in  psychic 
glycosuria,  the  blood-sugar  rising  to  0.4  or  0.5  per  cent,  and 
the  urine  containing  as  high  as  7.8  per  cent,  of  sugar.4 

The  urines  of  34  men  and  of  36  women  students  were 
tested  by  Folin5  before  and  after  college  examinations:  6 
men  and  6  women  showed  small  but  unmistakable  traces  of 
glycosuria  immediately  after  examination.  This  further  illus- 
trates the  phenomenon  of  emotional  glycosuria. 

Alimentary  glycosuria  is  seen  in  normal  animals  and  in 
man  when  sugar  is  given  in  larger  quantities  than  the  glycogen 
regulatory  function  can  care  for.     Moritz6  found  2  grams  of 

1  Araki:  "Zeitschrift  fur  physiologische  Chemie,"  1892,  xvi,  454;  see  also 
Wacker:   Ibid.,  1910,  lxvii,  197. 

2  Bohm  and  Hoffmann:  "Archiv  fur  exp.  Path,  und  Pharm.,"  1878,  viii, 
280. 

3  Cannon,  Shohl,  and  Wright:  "American  Journal  of  Physiology,"  191 1, 
xxix,  280. 

4  Hirsch  and  Reinbach:  "Zeitschrift  fur  physiologische  Chemie,"  1913, 
lxxxvii,  122. 

5  Folin,  Denis,  and  Smillie:  "Journal  of  Biological  Chemistry,"  1914,  xvii, 
519- 

6  Moritz:  "Verhandlungen  des  ioten  Congresses  fur  innere  Medizin,"  1891, 
p.  492. 

29 


450  '  SCIENCE   OF   NUTRITION 

glucose  in  the  urine  of  a  man  after  the  ingestion  of  200  grams. 
Such  an  alimentary  glycosuria  lasts  between  three  and  six 
hours. 

Moritz1  observed  0.2  to  0.3  per  cent,  of  sugar  in  the  urine  of 
4  out  of  6  healthy  people  who  had  partaken  of  a  quantity 
of  sweets  and  champagne. 

Evidently  such  conditions  as  these  are  not  to  be  classed 
with  diabetes  mellitus,  where  there  is  a  fundamental  disturb- 
ance in  the  sugar-burning  power  in  the  organism.  It  would 
be  of  service  to  distinguish  between  glycosurias  where  the 
sugar-holding  capacity  of  the  organs  has  been  diminished  or 
overstrained,  and  the  glycosuria  of  diabetes  in  which  the  sugar- 
burning  capacity  has  been  affected.  For  example,  Kleiner 
and  Meltzer2  injected  intravenously  4  grams  of  glucose  per 
kilogram  of  animal  into  both  normal  and  depancreatized  dogs. 
The  blood-sugar  rose  greatly  in  both  groups  of  animals,  but  in 
the  normal  animals  there  was  a  rapid  readjustment  through 
elimination  by  the  kidney,  glycogen  retention,  and  oxidation 
of  glucose,  whereas  in  the  depancreatized  animals,  though  re- 
moval of  the  glucose  by  the  kidney  was  active,  the  other  two 
functions  were  in  abeyance  and  the  blood-sugar  continued  at 
a  high  level  long  after  it  had  readjusted  itself  in  the  normal 
animals. 

A  special  type  of  glycosuria  is  caused  by  phlorhizin3  injec- 
tions, as  was  discovered  by  von  Mering.4  Here  the  blood  itself 
while  passing  through  the  kidney  loses  the  power  of  retaining 
its  normal  sugar  content  and  a  hypoglycemia  results.  Some- 
times when  the  kidney  is  altered  in  Bright's  disease  phlor- 
hizin is  ineffective  and  no  glycosuria  follows  its  administration. 
The  renal  character  of  phlorhizin  glycosuria  was  demonstrated 
by  Zuntz,5  who  placed  cannulas  in  the  upper  portions  of  the  two 

1  Moritz:  "Deutsches  Archiv  fur  klinische  Medizin,"  1890,  xlvi,  217. 

2  Kleiner  and  Meltzer:  "American  Journal  of  Physiology,"  1914-15,  xxxvi, 
361. 

3Lusk:  "Phlorhizinglukosurie,  Ergebnisse  der  Physiologie,"  1912,  xii,  372. 

4  von  Mering:  "Verhandlungen  des  sten  Congresses  fur  innere  Medizin," 
1886,  p.  185. 

5  Zuntz:   "Archiv  fur  Physiologie,"  1895,  p.  570. 


METABOLISM   IN  DIABETES   AND   PHOSPHORUS-POISONING     45 1 

kidneys  and  injected  phlorhizin  into  the  renal  artery  of  one. 
On  the  injected  side  sugar-containing  urine  appeared  in  two 
minutes,  and  three  minutes  later  the  kidney  on  the  opposite 
side  yielded  sugar  through  its  ureter.  The  delay  was  due  to 
the  lapse  of  time  necessary  for  the  transportation  of  the 
phlorhizin  by  the  blood-stream  from  the  injected  kidney  to  the 
other  one.  In  this  form  of  glycosuria  sugar  ingested  per  os,  or 
subcutaneously,  or  as  formed  in  protein  metabolism,  is  all 
eliminated  in  the  urine.1 

Extirpation  of  the  spleen  has  no  influence  upon  the  course 
of  phlorhizin  glycosuria.2  Nor  has  the  establishment  of  an 
Eck  fistula.3  An  Eck  fistula  is  one  which  diverts  the  whole 
of  the  portal  circulation  to  the  liver  into  the  inferior  vena 
cava,  and  leaves  the  liver  supplied  by  the  hepatic  artery 
only.  In  this  case  the  ingestion  of  glycocoll  by  the  animal 
resulted  in  its  complete  transformation  into  urinary  glucose, 
showing  that  the  diversion  of  blood  away  from  the  liver  in  no 
way  affected  the  synthetic  production  of  sugar  from  this 
amino-acid. 

Levene  found  that  the  bile  contained  a  small  amount  of 
glucose  after  the  administration  of  phlorhizin,  and  this  has 
been  confirmed  by  Woodyatt.4 

Loewi5  has  conceived  the  idea  that  the  blood-sugar  is  nor- 
mally in  a  loose  combination  with  colloid  substance.  This 
colloid  sugar  cannot  pass  through  the  glomerulus.  If,  how- 
ever, sugar  accumulates  in  the  blood  above  the  combining 
power  of  the  colloid,  then  the  crystalloid  glucose  readily  passes 
away  through  the  kidney.  This  condition  exists  in  diabetes 
mellitus.  In  phlorhizin  glycosuria  the  kidneys  break  up  the 
colloid  sugar,  and  the  sugar  may  then  be  eliminated.  Stiles 
and  Lusk,  while  accepting  Loewi's  theory,  have  added  the 
hypothesis  that  the  colloid  sugar  cannot  be  burned.     Phlorhi- 

1  Stiles  and  Lusk:    "American  Journal  of  Physiology,"  1903,  x,  67. 

2  Austin  and  Ringer:    "Journal  of  Biological  Chemistry,"  1913,  xiv,  139. 

3  Sweet  and  Ringer:   Ibid.,  p.  135. 

4  Woodyatt:   Ibid.,  1909-10,  vii,  133. 

6  Loewi:    "Archiv  fur  exp.  Path,  und  Pharm.,"  1902,  xlviii,  410. 


452  SCIENCE    OF   NUTRITION 

zin  acting  in  the  kidney  will  split  the  compound  and  permit  the 
elimination  of  sugar.  Any  free  glucose  in  the  general  circula- 
tion unites  with  the  colloid  radical  and  is  protected  from  com- 
bustion, as  is  the  case  when  5  grams  of  glucose  are  admin- 
istered subcutaneously,  only  to  reappear  in  the  urine  (Stiles 
and  Lusk).  The  presence  of  a  colloid-glucose  combination 
is  denied  by  Rosenfeld  and  Asher,1  who  find  that  the  sugar  of 
normal  blood  is  readily  diffusible. 

It  was  discovered  by  Ringer'2  that  when  a  large  quantity 
of  glucose  (75  grams)  is  given  to  a  phlorhizinized  dog  it  is  com- 
pletely eliminated  in  the  urine,  and  Lusk  found  that  the  inges- 
tion of  this  large  quantity  in  no  way  affects  the  respiratory 
quotient  (see  p.  244).  It  is  therefore  evident  that  the  com- 
pletely phlorhizinized  dog  has  lost  the  power  of  oxidizing 
glucose.  This  probably  does  not  occur  on  the  first  day  of  the 
administration  of  phlorhizin  and  may  possibly  be  due  to  the 
development  of  acidosis  (see  p.  261).  Stanley  Benedict3 
reports  that  administration  of  glucose  to  the  phlorhizinized 
dog  causes  the  amount  of  blood-sugar  to  rise  above  the  normal, 
which  shows  that  sugar  is  present  in  ample  concentration 
though  it  remains  chemically  untouched. 

Phlorhizin  glycosuria  is  only  temporary  in  character,  and 
subcutaneous  injections  of  alkaline  solutions  of  the  drug  three 
or  four  times  daily  have  been  employed  in  order  to  obtain 
constant  results. 

A  more  convenient  method  is  that  of  Coolen,4  who  no- 
ticed that  the  subcutaneous  injection  of  1  gram  of  phlorhizin 
suspended  in  7  c.c.  of  olive  oil  caused  a  glycosuria  of  maximal 
intensity  which  lasted  between  five  and  ten  days.  Common 
laboratory  practice  at  present  calls  for  daily  injections  of  this 
material. 

The  character  of  phlorhizin  glycosuria  has  been  dwelt  upon 

1  Rosenfeld  and  Asher:    "Zentralblatt  fur  Physiologie,"  1905,  xix,  449. 

2  Ringer:   "Journal  of  Biological  Chemistry,"  1912,  xii,  431. 

3Guion,  C.  M.,  and  Benedict,  S.  R.:  Paper  read  before  the  American 
Society  of  Biological  Chemists,  1915. 

4  Coolen:   "Archives  de  Pharmacodynamic,"  1895,  i,  267. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING    453 

because  the  protein  metabolism  is  here  identical  with  that 
observed  in  diabetes  mellitus. 

Von  Mering  and  Minkowski1  removed  the  pancreas  from 
dogs  and  obtained  a  condition  which  was  markedly  analogous 
to  diabetes  mellitus  in  man.  There  is  hyperglycemia  and  a 
large  excretion  of  glucose  in  the  urine ;  ingested  glucose  cannot 
be  burned,  but  is  completely  eliminated.  The  dogs  show  a 
considerable  acidosis  with  excretion  of  0-oxybutyric  acid,  and 
they  die  in  coma.2  If  a  portion  of  the  gland  remain  in  the 
abdominal  cavity  there  is  either  no  diabetes  or  only  a  partial 
diabetes.  Minkowski3  reports  that  if  a  piece  of  the  pancreas 
be  ingrafted  under  the  skin  of  a  dog  and  afterward  the  whole 
of  the  remainder  of  the  pancreas  be  removed  from  the  abdomen, 
the  dog's  urine  remains  free  from  sugar  for  two  months,  but 
on  extirpation  of  the  piece  ingrafted  under  the  skin  an  extreme 
diabetes  sets  in. 

Allen4  reports  that  a  dog  which  has  a  large  part  of  its 
pancreas  removed,  but  is  free  from  diabetes,  may  gradually 
become  diabetic  by  giving  protein  and  fat,  and  may  then 
manifest  the  spontaneous  downward  progress  observed  in 
human  patients. 

By  an  operation  which  united  the  blood  supply  of  two  dogs 
Forschbach5  established  the  condition  of  parabiosis.  On  the 
removal  of  the  pancreas  from  one  of  the  dogs  neither  developed 
diabetes.  An  analogous  experiment  is  that  of  Carlson,6  who 
performed  pancreatectomy  upon  bitches  near  to  term  and 
found  little  or  no  sugar  in  the  urine.  Here  the  embryo 
apparently  furnished  the  mother  with  the  substance  essential 
to  sugar  oxidation.  Murlin,  however,  in  unpublished  experi- 
ments finds  that  such  dogs  have  diabetic  respiratory  quotients 

1  von  Mering  and  Minkowski:  "Archiv  fur  exp.  Path,  und  Pharm.,"  1890, 
xxvi,  371. 

2  Allard:  Ibid.,  1908,  lix,  391. 

:i  Minkowski:   Ibid.,  1908,  Supplement-band,  p.  399. 

4  Allen,  F.  M.:  "Harvey  Lectures,"  1916-17. 

5  Forschbach:  "Archiv  fur  exp.  Path,  und  Pharm.,"  1909,  lx,  131. 

6  Carlson,  Orr,  and  Jones,  W.  S.:  "Journal  of  Biological  Chemistry,"  i9i4> 
xvii,  19. 


454  SCIENCE    OF   NUTRITION 

(0.69),  and  suggests  that  the  absence  of  glucose  from  the  urine 
is  due  to  carbohydrate  retention  by  the  fetus. 

It  has  long  been  known  that  diabetics  eliminate  sugar 
even  after  all  administration  of  sugar  is  stopped.  It  has 
also  been  generally  recognized  that  protein  ingestion  tends 
to  increase  the  sugar  output  in  the  urine,  while  fat  has  no 
effect. 

A  large  amount  of  information  has  been  collected  concern- 
ing the  relation  between  the  urinary  nitrogen  and  sugar 
elimination  in  the  fasting  and  meat-fed  diabetic  organism. 
The  dextrose  to  nitrogen  ratio  (D  :  N)  is  a  key  to  the  problem 
of  the  quantity  of  sugar  which  can  be  derived  from  protein 
metabolism  (p.  173). 

Minkowski1  was  the  pioneer  who  discovered  that  depan- 
creatized  dogs,  whether  fasting  or  fed  with  meat,  showed  a  con- 
stant elimination  of  2.8  grams  of  glucose  for  each  gram  of 
nitrogen  in  the  urine.  This  ratio  (D  :  N  :  :  2.8  :  1)  was  the 
average  obtained  from  7  dogs  on  twenty-two  different  days. 
The  lowest  ratio  was  2.62  :  1,  the  highest  3.05  :  1.  Some 
other  operators  have  been  unable  to  obtain  these  ratios. 
Pfliiger2  finds  a  variable  and  generally  lower  ratio,  and  his  dogs 
all  died  of  abscesses.  Embden's3  ratios  are  all  lower  than 
Minkowski's,  and  are  probably  due  to  incomplete  extirpation 
of  the  pancreas. 

The  accuracy  of  Minkowski's  results  is  indicated  by  the 
fact  that  the  ratio  (D  :  N  :  :  2.8  :  1)  may  be  easily  established 
by  the  administration  of  phlorhizin  to  rabbits,  goats,  cats,  and 
in  certain  dogs  whose  kidneys  have  been  somewhat  affected, 
as,  for  example,  by  giving  camphor.  Phlorhizin  acts  first  to 
cause  a  sweeping  out  of  the  excess  of  sugar  in  the  organism, 
with  a  subsequent  establishment  of  the  ratio.  (See  table,  p. 
463.)  The  ratios  in  different  animals  are  given  in  the  following 
table : 

1  Minkowski:  "Archiv  fur  exp.  Path,  und  Pharm.,"  1893,  xxxi,  pp.  85, 
97- 

2  Pfliiger:   "Das  Glycogen,"  1905,  p.  491. 

3  Embden  and  Salomon:   "Hofmeister's  Beitrage,"  1905,  vi,  63. 


METABOLISM    IN    DIABETES    AND    PHOSPHORUS-POISONING     455 
RATIOS  IN  DIABETES  OF  D  :  N  :  :  2.8  :  1 


Dog.1 

Dog.= 

CAT.' 

Goat.* 

Rabbit.5 

Day. 

Pancreas 
Diabetes. 

Phlorhizin 

and 
Camphor. 

Phlorhizin. 

Phlorhizin. 

Phlorhizin. 

Second  day  of  diabetes. 
Third  day  of  diabetes .  . 
Fourth  day  of  diabetes. 
Fifth  day  of  diabetes. .  . 
Dav  unknown 

2.SS 

2.04 

3-°9 

2.8 

2-93 

2.S0 

2-93 

2-95 
2.90 
2.78 

2.89 
2.69 

The  uniformity  of  the  ratio  as  shown  in  different  animals  is 
very  striking.  One  may  calculate  from  these  results  that  45 
per  cent,  of  the  protein  molecule  may  be  converted  into  dex- 
trose in  the  course  of  metabolism. 

This,  however,  does  not  complete  the  story  of  the  D  :  N 
ratio,  for  a  higher  ratio,  or  3.75  :  1,  was  discovered  by  Reilly, 
Nolan,  and  Lusk6  in  the  urine  of  dogs  with  normal  kidneys, 
after  subcutaneous  injections  of  phlorhizin.  This  ratio  was 
subsequently  revised  by  Stiles  and  Lusk7  and  found  to  be 
3.65  :  1.  The  importance  of  this  discovery  was  enhanced  by 
the  finding  of  Mandel  and  Lusk8  that  the  same  ratio  may  exist 
in  human  diabetes  when  the  patient  is  given  a  diet  of  meat  and 
fat.     The  ratios  found  on  successive  days  are  thus  comparable: 


zintzed  Dog. 

Phlorhizinized  Man. 

Diabetes  Mellitus  in  Man. 

3.609 

3o810 

3.6011                   3.7512 

3-65 

3.82 

3-65                      3o6 

3.66 

3-66 

3.66                      3.70 

3.62 

3-63 


3-68 


3-64 


3-66 


1  Minkowski:    Loc.  cit.,  p.  97. 

2  Jackson:   "American  Journal  of  Physiology,"  1902,  viii,  p.  xxxii. 

3  Arteaga:   Ibid.,  1901,  vi,  175. 

4  Lusk:   "Zeitschrift  fur  Biologie,"  1901,  xlii,  43. 

6  Reilly,  Nolan,  and  Lusk:  "American  Journal  of  Physiology,"  1898,  i,  396. 

6  Reilly,  Nolan,  and  Lusk:   Loc.  cit. 

7  Stiles  and  Lusk:   "American  Journal  of  Physiology,"  1903,  x,  67. 

8  Mandel  and  Lusk:  "Deutsches  Archiv  fur  k'lin.  Median,"  1904,  Ixxxi,  479. 

9  Stiles  and  Lusk:    Loc.  cit.,  p.  77.     (Details,  this  book,  p.  99.) 

10  Benedict,  S.  R.,  and  Lewis,  R.  C:    "Proceedings  of  the  Society  for  Ex- 
perimental Biology  and  Medicine,"  1914,  xi,  134.     (Details  unpublished.) 

11  Mandel  and  Lusk:    Loc.  cit.,  p.  479. 

12  Greenwald:   "Journal  of  Biological  Chemistry,"  1913-14,  xvi,  375. 


456  SCIENCE   OF   NUTRITION 

In  another  place  (p.  174)  it  has  been  shown  that  the  D  :  N 
ratio  does  not  vary  after  the  ingestion  of  sufficient  meat  to 
double  the  quantity  of  nitrogen  in  the  urine;  the  sugar  also 
doubles.  The  sugar  production  is  therefore  proportional  to 
the  protein  metabolism,  and,  apparently,  must  be  derived 
from  protein. 

Various  objections  have  been  raised  to  this  statement. 
Other  experiments,  however,  confirm  the  above  proposition. 

Liithje1  gave  "nutrose"toadepancreatizeddog.  "Nutrose" 
contains  casein,  but  no  sugar.  The  dog  weighed  5.8  kilograms 
and  eliminated  n  76  grams  of  glucose  during  twenty-five  days. 
The  tissues  of  the  dog  could  not  possibly  have  contained  over 
232  grams  of  glycogen  at  the  beginning  of  the  experiment.  The 
source  of  the  sugar  could  not  have  been  the  animal's  store  of 
glycogen,  but  it  must  have  arisen  from  either  protein  or  fat. 

The  D  :  N  ratio  of  3.65  :  1  was  accepted  by  Lusk  as  being 
true  for  the  dog  because  the  greater  number  of  the  higher 
ratios  which  were  found  were  established  at  this  level.  Janney2 
prefers  to  take  the  average  of  all  determined  D  :  N  ratios  and 
in  this  way  arrives  at  a  ratio  of  3.43  :  1.  He  argues  that, 
since  4.7  per  cent,  of  the  urinary  nitrogen  is  in  the  form  of 
creatin  and  creatinin,  which  are  not  glucose  formers,  a  cor- 
rection would  bring  up  the  D  :  N  ratio  in  the  dog  to  3.60. 
Although  it  is  not  clear  why  the  urinary  creatin  and  creatinin 
should  be  thus  subtracted,  for  they  are  as  truly  metabolism 
products  of  protein  as  is  urea,  still  Janney's3  experiments, 
which  show  the  quantities  of  glucose  produced  from  various 
forms  of  flesh,  as  determined  through  feeding  experiments 
with  the  phlorhizinized  dog,  are  of  great  interest  and  may  thus 
be  presented : 

Species  of  Flesh.                  Man.  Dog.  Rabbit.  Ox.  Chicken. 

D  :  N  ratio 3.6             3.6  3.8  3.6  3.4 

Glucose  per  100  gm.  of  pro- 
tein metabolized 58  58  60  58  54 

1  Liithje:    "Pfliiger's  Archiv,"  1905,  cvi,  160. 

2  Janney  and  Csonka:   "Journal  of  Biological  Chemistry,"  1915,  xxii,  203. 
s  Janney  and  Blatherwick:    Ibid.,  1915,  xxiii,  77. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING     457 

According  to  Janney,1  the  percentage  quantity  of  glucose 
derivable  from  the  following  proteins  is:  casein  48,  ovalbumin 
54,  serum  albumin  55,  gelatin  65,  fibrin  53,  edestin  65,  gliadin 
80,  and  zein  53  per  cent. 

Pfliiger2  would  have  it  that  fat  metabolism  is  the  principal 
source  of  sugar  in  diabetes. 

Giving  fat  with  meat  to  a  diabetic  will  not  ordinarily  in- 
crease the  sugar  in  the  urine.  The  writer  has  never  observed 
such  an  increase  in  any  of  the  work  of  his  laboratory.  A 
large  production  of  sugar  from  fat  has  been  elsewhere  reported,3 
and  Cremer4  finds  that  glycerin  alone  will  increase  the  output 
of  sugar  in  the  urine.     (See  p.  262.) 

On  giving  meat  in  diabetes  the  fat  metabolism  is  reduced 
as  it  would  be  in  the  normal  organism,  and  yet  there  is  no 
effect  on  the  D  :  N  ratio,  and  therefore  the  latter  cannot  be 
influenced  by  the  quantity  of  fat  burned.  This  is  shown  in  a 
respiration  experiment  made  by  Mandel  and  Lusk5  on  a  dog 
with  phlorhizin  glycosuria  whose  metabolism  starving  and  after 
meat  ingestion  was  as  follows : 

Calories 
from         Calories     Calories, 
D  :  N.        Protein,     from  Fat.       Total. 

Fasting 3.69  80.2  274.4         354.6 

300  grams  meat 3.55  161. 9  261.7         423.6 

The  protein  metabolism  doubled  when  meat  was  ingested, 
the  fat  metabolism  fell,  but  the  D  :  N  ratio  remained  constant. 

It  has  also  been  demonstrated  that  neither  exposure  to  cold 
nor  mechanical  exercise,  both  of  which  result  in  a  largely  in- 
creased metabolism  of  fat,  has  any  effect  on  the  sugar  output 
in  pancreas  diabetes6  or  in  phlorhizin  glycosuria.7  Freund 
and  Marchand8  found  that  ten  hours'  exposure  to  the  winter's 

1  Janney:   "Journal  of  Biological  Chemistry,"  1915,  xx,  321. 

2  Pfliiger:  "Pfliiger's  Archiv,"  1905,  cviii,  115. 

3  Hartogh  and  Schumm:  "Archiv  fur  exp.  Path,  und  Pharm.,"  1901,  xlv,  11. 

4  Cremer:    "Miinchener  med.  Wochenschrift,"  1902,  xlix,  944. 

5  Mandel  and  Lusk:    "American  Journal  of  Physiology,"  1903,  x,  54. 
6Allard:   "Archiv  fur  exp.  Path,  und  Pharm.,"  1908,  lix,  111;  Seo,  Ibid., 

P-  34i- 

7  Lusk:    "American  Journal  of  Physiology,"  1908,  xxii,  163. 

8  Freund  and  Marchand:  "Archiv  fur  exp.  Path,  und  Pharm.,"  1913,  lxxiii, 
276. 


458  SCIENCE   OF   NUTRITION 

cold  reduced  the  blood-sugar  of  a  phlorhizinized  dog  to  zero. 
The  writer  found  in  a  phlorhizinized  dog  which  had  been  rid  of 
glycogen  by  shivering  and  exercise  that  the  composition  of 
the  urine  was  unchanged  as  the  result  of  traveling  1500 
meters  in  a  revolving  wheel,  an  effort  which  would  have  more 
than  doubled  the  metabolism  of  fat  during  the  hour  when  the 
exercise  was  taken.  The  analytic  data  for  two-hour  periods 
were  the  following: 

Glucose.    Nitrogen.       D  :  N. 

Rest 4-57  1-26  3.63 

Work,  1500  meters  during  first  hour  4.62  1.26  3.67 

In  this  experiment  exercise  was  without  influence  on  the 
excretion  of  nitrogen.  If,  however,  the  animal  contains 
residues  of  glycogen  which  as  a  result  of  exercise  are  converted 
into  sugar  and  eliminated,  then  there  is  also  an  increased 
nitrogen  elimination  as  the  result  of  work.  This  is  suggestive 
of  a  chemical  union  between  glycogen  and  nitrogenous  sub- 
stances. 

The  theory  of  the  origin  of  sugar  from  fat  was  supported  by 
Falta,1  who  found  a  largely  increased  sugar  output  after 
administering  adrenalin  to  dogs  with  pancreas  diabetes. 
Among  the  cases  of  high  D  :  N  in  human  diabetes  reported 
from  von  Noorden's  clinic  that  described  by  Bernstein, 
Bolafrio,  and  Westenrijk2  is  the  most  remarkable.  The  ratio, 
after  deducting  the  carbohydrates  ingested  in  the  food,  often 
reached  D  :  N  :  :  10  :  1.  The  high  ratios  in  diabetes  are 
explained  by  Falta  as  being  due  to  very  great  activity  on  the 
part  of  the  adrenals  which  not  only  inhibits  the  internal 
secretion  of  the  pancreas,  but  also  causes  a  production  of 
sugar  from  fat.  However,  Ringer,3  working  in  the  author's 
laboratory,  finds  that  if  adrenalin  be  administered  to  a  fasting 
phlorhizinized  dog,  although  the  first  administration  of  the 
drug  may  bring  about  an  elimination  of  "extra  sugar"  which 

1  Eppinger,  Falta,  and  Rudinger:  "Zeitschrift  fur  klinische  Medizin," 
iqo8,  lxvi,  1. 

2  Bernstein,  Bolafno,  and  Westenrijk:   Ibid.,  1908,  lxvi,  378. 

3  Ringer:   "Journal  of  Experimental  Medicine,"  1010,  xii,  105. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING     459 

may  be  discharged  from  the  glycogen  repositories  of  the  body 
on  account  of  the  anemia  of  the  tissues  (see  p.  447),  a  second 
injection  of  adrenalin  may  be  entirely  without  influence  on 
either  the  sugar  or  nitrogen  elimination.  This  indicates 
that  adrenalin  does  not  cause  a  production  of  sugar  from  fat. 

The  high  D  :  N  ratios  reported  above,  as  well  as  many 
similar  observations  described  in  the  literature,  are  unques- 
tionably due  to  the  surreptitious  ingestion  of  food  containing 
carbohydrate. 

Falta  explains  the  results  of  many  experiments  by  stating 
that  while  the  secretory  activities  of  thyroid  and  adrenals  are 
each  stimulated  by  the  secretions  of  the  other,  the  activity  of 
the  pancreas  is  in  like  manner  inhibited  by  the  secretions  of 
the  other  two  glands.  Therefore  supersecretion  of  adrenalin 
inhibits  the  secretory  function  of  the  pancreas  so  that  the 
organism  can  no  longer  oxidize  carbohydrates,  and  at  the  same 
time  it  stimulates  the  thyroid,  causing  increased  protein 
metabolism.  Furthermore,  in  exophthalmic  goiter,  where 
there  is  supersecretion  in  the  thyroid  gland,  there  is  a  tendency 
to  glycosuria,  and  it  is  believed  that  true  diabetes  has  been 
induced  by  this  cause.1  Administration  of  thyroid  extracts  to 
dogs  also  produces  glycosuria.  Cecil,2  working  under  Opie's 
direction,  finds  lesions  of  the  pancreas  in  cases  of  diabetes 
associated  with  exophthalmic  goiter,  and  Forschbach  and 
Severin,3  in  Minkowski's  clinic,  believe  that  there  is  very- 
likely  a  slight  disturbance  of  the  pancreas  in  some  cases  of 
hyperthyroidism. 

The  complicated  theorizing  of  the  von  Noorden  school, 
as  represented  by  Falta's  statements,  found  early  acceptance 
among  clinicians.  However,  there  are  many  demonstrable 
errors  in  the  presentation.  Thus  Ringer,  in  the  experiments 
mentioned  above,  found  no  increase  in  the  protein  metabolism 

1  Magnus-Levy:  von  Noorden's  "Handbuch  des  Stoffwechsels,"  1907, 
Bd.  ii,  p.  333- 

2  Cecil:    "Journal  of  Experimental  Medicine,"  iqoq,  xi,  266. 

3  Forschbach  and  Severin:  "Archiv  fiir  exp.  Path,  und  Pharm.,"  19 14,  lxxv, 
168. 


460  SCIENCE   OF   NUTRITION 

of  his  dogs  after  giving  them  epinephrin,  and  Lusk1  found  the 
same  to  be  true  in  normal  dogs,  and  also  discovered  that  if 
glucose  were  given  to  normal  dogs  and  then  epinephrin  were 
administered  the  respiratory  quotient  rose  to  unity,  showing  a 
normal  combustion  of  carbohydrate. 

Fuchs  and  Roth2  state  that  the  respiratory  quotient  in- 
creases in  human  beings  after  the  subcutaneous  injection  of 
epinephrin,  as  appears  below: 


Before. 

Epinephrin. 

After. 

0.85 
0.87 

o.gi 
o.g6 

0.84 
0.86 

It  is  evident  that  the  theory  that  epinephrin  causes  a 
production  of  sugar  from  fat,  decreases  the  power  of  the  organ- 
ism to  oxidize  glucose  through  inhibition  of  pancreatic  func- 
tion, and  stimulates  the  thyroid  so  that  protein  metabolism 
is  increased,  is  untenable  in  any  of  its  particulars. 

In  the  matter  of  the  thyroid  being  the  cause  of  the  high 
protein  metabolism  in  diabetes,  von  Noorden  is  right.  Ep- 
pinger,  Falta,  and  Rudinger3  extirpated  both  pancreas  and 
thyroid  and  found  that  the  protein  metabolism  was  almost  the 
same  as  in  the  normal  dog  instead  of  being  increased  three- 
or  fourfold,  as  occurs  when  the  pancreas  alone  is  extirpated. 
The  D  :  N  ratio  was  at  first  3.5,  but  declined  after  a  few  days  to 
2.8. 

Von  Noorden  suggested  to  the  writer  of  this  book  that  the 
increased  total  metabolism  which  follows  the  administration  of 
phlorhizin  (see  p.  474)  would  not  take  place  if  the  thyroid 
gland  had  been  previously  extirpated.  Lusk4  determined  the 
metabolism  of  a  dog  after  complete  thyroidectomy  with  re- 
moval of  three  parathyroids  and  found  it  to  be  19  calories  per 
hour,  whereas  after  phlorhizin  administration  values  of  20.3 

1  Lusk:   "Archives  of  Internal  Medicine,"  1014,  xiii,  673. 

2  Fuchs  and  R6th:   "Zeitschrift  fur  ex.  Path,  und  Ther.,"  1012,  x,  187^ 

3  Eppinger,  Falta,  and  Rudinger:  "Zeitschrift  fur  klinische  Medizin," 
1908,  lxvi,  1. 

4  Lusk:  Proceedings  of  the  XVIIth  International  Congress  of  Medicine, 
Section  on  Physiology,  London,  1913,  p.  13. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING     46 1 

and  19.3  calories  per  hour  were  found,  determined  one  and 
three  days  after  diabetes  had  been  induced.  The  usual  rise  in 
protein  metabolism  and  total  metabolism  were  absent.  After 
the  ingestion  of  meat,  however,  the  heat  production  increased 
and  rose  on  one  occasion  from  a  basal  value  of  17.5  to  26 
calories  per  hour,  an  increase  of  50  per  cent.  The  urinary- 
nitrogen  largely  increased  and  the  process  of  amino-acid 
stimulation  was  in  full  play,  notwithstanding  the  absence  of 
the  thyroid  gland.  This  naturally  suggests  the  hypothesis 
that  the  reason  why  there  is  no  increased  heat  production  in 
diabetes  after  thyroidectomy  is  that  there  is  no  rise  in  the 
quantity  of  protein  metabolized. 

As  shown  by  Parhon  and  by  Cramer  (see  p.  442),  thyroid 
ingestion  causes  the  liver  to  discharge  glycogen.  Conversely, 
after  thyroid  extirpation  the  liver  should  retain  glycogen  more 
tenaciously  than  before.  This,  at  least,  would  explain  the 
long  continued  high  D  :  N  ratios  observed  by  Lusk  in  phlo- 
rhizinized  dogs  after  thyroidectomy  and  by  Miura1  in  rabbits 
similarly  treated. 

In  contradiction  to  the  statements  of  Eppinger,  Falta, 
and  Rudinger,  and  of  Miura,  Underbill2  finds  that  epinephrin 
glycosuria  may  be  as  easily  produced  in  thyroidectomized  as  in 
normal  animals. 

The  subject  of  the  correlation  between  the  various  glands 
of  internal  secretion  is  evidently  one  as  replete  with  oppor- 
tunities for  the  play  of  the  imagination  as  it  is  for  enlighten- 
ing experimental  research. 

A  question  of  special  interest  is  the  cause  of  the  two  D  :  N 
ratios,  2.8  :  1  and  3.65  :  1.  The  former  represents  a  production 
of  45  per  cent.,  the  latter  one  of  58  per  cent,  of  sugar  from  meat 
protein.  In  neither  case  can  ingested  glucose  be  burned. 
It  is,  of  course,  possible  that  the  sugar  production  varies  under 
different  circumstances;  that  is  to  say,  the  organism  (liver?) 
may  be  able  at  times  to  produce  sugar  from  a  certain  class  of 

1  Miura:   "Biochemische  Zeitschrift,"  1913,  li,  423. 

2Underhill:   "American  Journal  of  Physiology,"  iqio-ii,  xxvii,  331. 


462  SCIENCE    OF   NUTRITION 

protein  decomposition  products,  and  at  other  times  not.  For 
example,  it  has  been  noted  (p.  201)  that  glutamic  acid  is 
convertible  into  glucose  in  the  dog,  but  Neuberg1  testifies 
that  it  may  also  be  converted  into  butyric  acid  from  which 
sugar  cannot  be  formed.  Or,  one  may  adopt  the  hypothesis  of 
Mandel  and  Lusk,2  which  assumes  a  difference  between 
a-colloid  glucose  and  /3-colloid  glucose  existing  in  the  blood. 
By  a-glucose  is  understood  the  amount  of  glucose  represented 
by  the  ratio  D  :  N  :  :  2.8  :  1,  or  45  per  cent,  of  the  protein. 
The  /3-glucose  represents  the  additional  13.6  per  cent,  of  the 
protein,  when  the  ratio  3.65  :  1  is  present.  The  ratio  would 
depend  on  the  combustion  or  non-combustion  of  the  /3-glucose. 
If  the  latter  burns,  it  must  do  so  as  a  complex,  for  as  free 
glucose  it  would  be  eliminated  in  the  urine. 

This  theory  of  a  difference  in  chemical  union  would  explain 
the  fact  discovered  by  Straub3  for  carbon  monoxid  "diabetes" 
and  by  Seelig4  for  glycosuria  following  ether  inhalation,  that 
sugar  appears  in  the  urine  in  large  quantity  if  a  dog  be  fed 
with  meat,  but  disappears  if  the  animal  be  given  carbohydrate 
alone.  Seelig  found  no  glycosuria  when  an  intravenous  in- 
fusion of  oxygen  was  administered  at  the  same  time  that 
ether  was  given.  It  may  be  that  lack  of  oxygen  causes  a 
dissociation  of  either  a-  or  /3-colloid  glucose  derived  from 
protein,  which  glucose  then  appears  in  the  urine.  This 
suggestion  is,  however,  highly  speculative. 

One  of  the  very  pronounced  characteristics  of  the  diabetic 
is  his  constant  emaciation.  There  is  usually  a  larger  excretion 
of  nitrogen  in  the  urine  than  is  necessary  for  a  healthy  person. 
It  may  be  recalled  that  carbohydrates  diminish  the  protein 
metabolism,  and  also  that  a  person  may  support  life  on  meat 
and  fat  alone  without  tissue  waste.  But  in  this  latter  case 
there  is  a  supply  of  carbohydrate  derived  from  protein  metab- 

1  Brasch  and  Neuberg:   "Biochemische  Zeitschrift,"  1908,  xiii,  299. 

2  Mandel  and  Lusk:  "Deutsches  Archiv  fur  klinische  Medizin,"  1904, 
lxxxi,  491. 

3  Straub:   "Archiv  fur  exp.  Path,  und  Pharm.,"  1897,  xxxviii,  139. 

4  Seelig:   Ibid.,  1905,  lii,  481. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING     463 

olism.  This  is  also  true  in  starvation.  But  when  the  protein 
sugar  is  withdrawn  from  the  tissue  cells  in  diabetes,  there  is  at 
once  a  largely  increased  protein  metabolism.  This  is  most 
obvious  in  fasting  animals  treated  with  phlorhizin,  as  the 
glycosuria  can  be  immediately  induced.  The  increase  in 
protein  metabolism  is  most  marked  where  the  higher  D  :  N 
ratio  exists.  In  this  connection  the  following  experiments  on 
fasting  animals  are  suggestive: 


TABLE    ILLUSTRATING    THE    INFLUENCE    OF    DIABETES    ON 
PROTEIN   METABOLISM 


GOAT.' 

Doc2 

D. 

N. 

D  :N. 

D. 

N. 

D  :N. 

Fasting 

20.33 
26.08 

23-39 
19.01 

3-72 
3-71 
4.90 
8.83 
8.06 
6.84 

4-15 
2-95 
2.90 

2.78 

63-55 

65-30 
65.84 
64.80 

4.04 

4.17 

12.66 

18.76 

18.57 
17.29 

Fasting 

Fasting  and  diabetic .  .  . 
«                  << 

5.02 
3.38 
3-54 

3-74 

In  the  goat  the  protein  metabolism  rose  to  238,  in  the  dog  to 
450  per  cent,  of  that  in  the  normal  animals,  as  the  result  of  the 
loss  of  the  influence  of  the  small  quantity  of  protein  sugar 
produced  in  starvation. 

Falta,  Grote,  and  Staehelin3  found  increases  in  the  protein 
metabolism  of  fasting  dogs  which  had  been  depancreatized, 
equal  to  three-  and  fivefold  the  normal  amount. 

In  the  case  of  diabetes  mellitus  reported  by  Mandel  and 
Lusk  where  the  ratio  D  :  N  was  3.65  :  1,  it  was  found  that  the 
ingestion  of  broths  containing  7.7  grams  of  nitrogen  was  fol- 
lowed by  an  elimination  of  21.7  grams  of  nitrogen  in  the  urine 
or  a  loss  of  body  nitrogen  approximating  14  grams.  The 
patient  was  greatly  emaciated,  and  passed  this  day  in  bed. 


1  Lusk:    "Zeitschrift  fur  Biologie,"  1901,  xlii,  43. 

2  Reilly,  Nolan,  and  Lusk:  "American  Journal  of  Physiology,"  1898,  i,  397. 

3  Falta,  Grote,  and  Staehelin:    "Hofmeister's  Beitrage,"  1907,  x,  199. 


464  SCIENCE   OF   NUTRITION 

He  could  not  be  maintained  in  nitrogen  equilibrium  with 
19  grams  of  protein  nitrogen  in  the  food,  but  was  in  nitrogen 
equilibrium  when  given  27  grams.  In  all  cases  of  intense 
diabetes  this  factor  of  an  increased  protein  metabolism  must 
be  considered.  In  mild  cases  in  which  sugar  disappears  from 
the  urine  when  carbohydrates  are  cut  out  of  the  food,  and  in 
which  the  patient  may  burn  his  protein  sugar,  the  protein 
metabolism  is  not  different  from  that  of  a  normal  person 
living  on  meat  and  fat. 

As  would  be  expected  under  conditions  involving  an  in- 
crease in  protein  metabolism,  amino-acids  are  found  in 
increased  quantities  in  both  blood  and  urine  of  diabetic 
patients.1 

The  preeminence  of  fat  metabolism  in  the  diabetic  as  the 
mainstay  of  his  organism  leads  to  inquiry  as  to  the  origin  of 
the  fatty  acid  called  /3-oxybutyric  acid,  and  of  aceto-acetic  acid 
and  aceton  which  are  directly  derived  from  it.2  Whence  do 
these  aceton  bodies  arise?  They  were  at  first  supposed  to 
come  from  glucose,  following  a  chemical  process  analogous  to 
the  butyric  acid  fermentation  of  carbohydrates,  but  it  was 
soon  discovered  that  in  normal  persons  the  aceton  bodies  were 
especially  found  in  the  fasting  state.  Many  then  attributed 
the  presence  of  aceton  to  the  specific  breakdown  of  body 
protein,  since,  when  protein  was  given  in  the  food,  the  aceton 
bodies  disappeared  in  the  urine.  However,  Magnus-Levy3  has 
reported  a  case  of  a  boy  in  coma  who  eliminated  an  average  of 
97.5  grams  of  /3-oxybutyric  acid  and  aceto-acetic  acid  daily 
for  three  days  in  addition  to  an  unmeasured  quantity  of  aceton 
in  the  breath,  and  during  this  time  the  protein  metabolism 
amounted  to  90  grams,  of  which  latter  at  least  40  grams  ap- 
peared as  sugar  in  the  urine.  The  97.5  grams  of  aceton 
bodies  in  this  case  could  not  have  been  entirely  derived  from 

1  Galambos  and  Tausz:  "Zeitschrift  fur  klin.  Med.,"  1913,  lxxvii,  14;  1914, 
Ixxx,  381.     Loffler:    Ibid.,  1913,  lxxviii,  483. 

2  This  description  is  taken  from  Lusk:  "Metabolism  in  Diabetes,"  Harvey- 
Society  Lecture,  "Archives  of  Internal  Medicine,"  1909,  iii,  1. 

3  Magnus-Levy:   "Ergebnisse  d.  inn.  Med.,"  1908,  i,  374. 


METABOLISM    IN   DIABETES    AND    PHOSPHORUS-POISONING     465 

the  90  grams  of  protein,  but  they  must  have  originated  largely 
from  fat. 

Stadelman1  first  pointed  out  the  relationship  between  the 
formation  of  j8-oxybutyric  acid  and  the  occurrence  of  coma. 
Coma  has  been  compared  to  the  sword  of  Damocles  which 
hangs  suspended  over  every  diabetic.  It  has  been  discovered 
that  whenever  the  organism  is  thrown  suddenly  from  a  carbo- 
hydrate regimen  to  a  combustion  of  fat  the  aceton  bodies 
appear  in  the  urine.  This  condition  is  greatly  intensified  in 
diabetes  when  even  the  sugar  derived  from  protein  is  not 
burned. 

Each  molecule  of  butyric  acid  can  yield  one  of  /3-oxybutyric 
acid.  It  has  been  calculated  by  Magnus-Levy2  that  ioo  grams 
of  neutral  fat  made  of  stearin,  palmitin,  and  olein  may  yield 
36.2  grams  of  /3-oxybutyric  acid.  It  is  therefore  evident  that 
the  higher  fatty  acids  are  the  more  valuable  nutriment. 
Butter,  with  its  high  content  of  butyric  acid,  largely  increases 
the  output  of  the  aceton  bodies  in  diabetes;  50  to  100 
grams  of  butter  fat  when  administered  to  a  diabetic  may  raise 
his  urinary  aceton  four-  to  eightfold.3  Oleomargarin  is  to  be 
preferred. 

Magnus-Levy4  gave  11.7  grams  of  /3-oxybutyric  acid  to  a 
normal  dog.  This  was  completely  burned.  He  then  gave 
1 1. 5  grams  to  a  phlorhizinized  dog,  with  the  result  that  there 
was  an  increased  elimination  of  7.6  grams  of  /3-oxybutyric 
acid  and  aceton.  Since  some  aceton  was  eliminated  in  the 
breath,  it  is  evident  that  the  animal  had  largely  lost  the  power 
to  burn  ingested  /3-oxybutyric  acid. 

The  evidence  concerning  the  formation  of  the  aceton 
bodies  from  fat  and  from  some  amino-acids  has  already  been 
discussed  (see  p.  208).  It  suffices  here  to  recall  that  Otto 
Neubauer5  found  that  the  ingestion  of  either  /3-oxybutyric 

1  Stadelman:  "Experimentelle-klinische  Untersuchungen,"  Stuttgart,  1890. 

2  Magnus-Levy:    "Ergebnisse  d.  inn.  Med.,"  1908,  i,  384. 

3  Fejes:    "Magyar  orvosi  Archivum,"  1907,  viii,  335. 

4  Magnus-Levy:    "Ergebnisse  d.  inn.  Med.,"  1908,  i,  372. 

6  Neubauer,  O.:  "Verhandlungen  des  deutschen  Congresses  fur  innere 
Medizin,"  1910,  xxvii,  566. 

3° 


466 


SCIENCE    Of    NUTRITION 


acid  or  aceto-acetic  acid  by  a  diabetic  patient  always  caused 
the  partial  excretion  of  the  one  given  in  the  form  of  the 
other.     The  reaction  is  reversible: 

CH3.CHOH.CH2.COOH  +  O^CH3.CO.CH2.COOH  +  H20. 

In  marked  acidosis  Neubauer  found  that  /3-oxybutyric  acid 
amounted  to  between  60  and  80  per  cent,  of  the  total  urinary 
aceton  bodies. 

If  a  surviving  liver  be  perfused  with  blood  containing 
/3-oxy butyric  acid,  the  latter  is  in  part  converted  into  aceto- 
acetic  acid.1  Minced  liver  or  even  the  aqueous  extract  of 
liver  tissue  will  effect  the  same  reaction.2 

Fischler  and  Kossow3  report  that  the  formation  of  aceton 
bodies  in  a  phlorhizinized  dog  is  decreased  in  the  presence  of 
an  Eck  fistula,  whereas  if  a  "reversed"  Eck  fistula  be  created 
by  diverting  the  blood  from  the  vena  cava  into  the  portal 
vein,  the  excretion  of  aceton  bodies  is  increased  fivefold. 
This  points  to  the  liver  as  the  main  source  of  the  aceton 
bodies,  if  one  may  accept  conclusions  drawn  from  experi- 
mental conditions  so  profoundly  abnormal. 

The  quantity  of  the  aceton  bodies  in  the  blood  is  given  by 
Marriott4  as  follows: 


Normal  dog 


Normal  child 


Phlorhizinized  dog 
Diabetic  child  in  coma 


1  Embden  and  Engel:   "Hofmeister's  Beitrage,"  1908.  xi.  323. 

2  Wakeman  and  Dakin:    "Journal  of  Biological  Chemistry."'  1909,  vi,  373. 

3  Fischler  and  Kossow:   "Deutsche*  Archiv  fur  klin.  Med. ,"1913,  cxi,  479. 

4  Marriott:    "Journal  of  Biological  Chemistry,"  1913-14,  xvi,  293. 


METABOLISM   IN  DIABETES   AND   PHOSPHORUS-POISONING     467 

The  increase  in  the  aceton  bodies  in  the  blood  is  greatest 
in  diabetes  mellitus  in  man,  is  not  so  marked  in  phlorhizin 
glycosuria  in  dogs,  and  is  least  of  all  present  in  depancreatized 
dogs.  Sassa1  states  that  the  organs  of  diabetic  men  dying  in 
coma  may  contain  eight  times  the  normal  quantity  of  /3-oxy- 
butyric  acid,  the  liver  showing  relatively  the  greatest  storage 
of  the  substance.  In  one  instance  (Case  II)  130  milligrams  of 
/3-oxybutyric  acid  were  found  in  100  grams  of  the  body  tissue 
of  a  man  weighing  70  kilograms,  and  the  author  computes  the 
presence  of  85  grams  of  the  substance  within  the  body. 
Marriott's2  highest  figures  for  100  c.c.  of  diabetic  blood  in  man 
are  28  milligrams  of  aceto-acetic  acid  and  45  milligrams  of 
0-oxybutyric  acid. 

The  demonstration  by  Ringer3  that  propionic  acid  was 
completely  converted  into  glucose  and  that  higher  fatty  acids 
with  uneven  numbers  of  carbon  atoms  yielded  glucose  in  so 
far  as  they  might  form  propionic  acid  by  /3-oxidation,  presents 
the  theoretic  possibility  of  giving  to  diabetics  fats  containing 
these  fatty  acids,  which  would  yield  innocuous  glucose  instead 
of  acid  bodies  as  the  end-products  of  oxidation.  Practical 
difficulties  in  the  preparation  of  such  fats  have  alone  prevented 
Ringer  from  testing  the  efficiency  of  their  administration  to 
diabetic  subjects. 

The  result  of  the  formation  of  acid  bodies  in  the  organism 
leads  to  a  condition  of  acidosis,  the  alkali  reserves  being  called 
upon.  Not  only  does  ammonia  increase  in  the  urine,  but  there 
may  be  a  marked  fall  in  the  carbon  dioxid  content  of  the 
blood  due  to  a  diminution  in  the  quantity  of  bicarbonate  of 
soda.  Magnus-Levy4  reports  an  extreme  case  in  which  100 
c.c.  of  the  blood  of  a  diabetic  just  before  death  in  coma 
contained  only  3.3  c.c.  of  carbon  dioxid  instead  of  40  c.c. 
normally  present. 

1  Sassa:    "Biochemische  Zeitschrift,"  1913-14,  1L\,  362. 

2  Marriott:    "Journal  of  Biological  Chemistry,"  1914,  xviii,  507. 

3  Ringer:   Ibid.,  191 2,  xii,  511. 

*  Magnus-Levy:  "Archiv  fur  experimentelle  Path,  und  Pharm.,"  iqoi, 
xlv,  389. 


468 


SCIENCE   OF   NUTRITION 


The  reduction  in  the  carbon  dioxid  combining  power  of 
the  blood  and  the  consequent  lowering  of  the  carbon  dioxid 
tension  in  the  alveoli  do  not  appear  in  the  earlier  days  of 
acidosis,  provided  the  acids  formed  be  neutralized  with  am- 
monia.1 The  withdrawal  of  alkali  occurs  later.  Rona  and 
Wilenko2  find  that,  despite  the  acidosis,  the  hydrogen  ion 
concentration  of  the  blood  may  remain  normal  on  account  of 
the  compensation  brought  about  through  the  removal  of 
carbon  dioxid  by  the  lungs  and  of  acids  through  the  urine. 
Notwithstanding  this  control  over  the  blood,  the  authors 
believe  it  possible  that  there  may  be  a  local  increase  of  the 
hydrogen  ion  concentration  in  certain  cells  and  tissues. 

Concrete  cases  of  blood  analyses  are  offered  by  Poulton3 
(see  p.  221),  who  reports  concerning  the  blood  of  7  diabetic 
patients.  The  first  6  possessed  a  normal  blood  reaction.  One 
of  them  (E.  M.  S.)  following  the  first  examination  fell  into 
deep  coma  and  twenty-two  hours  later  showed  an  abnormally 
high  hydrogen  ion  concentration.  E.  H.,  whose  blood  reaction 
was  similar,  was  also  in  deep  coma.  The  first  two  patients 
gave  no  indication  of  coma,  but  all  the  others  were  drowsy. 
B.  died  in  coma  eighteen  hours  after  the  examination  of  his 
blood,  which  had  been  normal  in  reaction. 

The  figures  are  in  part  as  follows: 


Patient. 

Alveolar  CO2. 

PH- 

Sodium 
Bicarbonate 
Daily. 

E.  R 

Mm. 
38.3 
22.O 
18.6 
16.8 

i5-i 

12. 1 

8.1 

7-3 

-7-33 
-7-25 
-7-36 
-7-36 
-7-33 
-7-35 
—  7.19 
-7.18 

Grams. 
0 

B.  K 

45 

F.  B 

II 

M.  T 

6 

E.S.M.1 

B.              

8 
45 

E.  H. 

60 

E.  S.  M 

45 

1  Munzer:   "Zeitschrift  fiir  exp.  Path,  und  Therapie,"  1914,  xvi,  281. 

2  Rona  and  Wilenko:    "Biochemische  Zeitschrift,"  1913-14,  lix,  173. 

3  Poulton:   "Journal  of  Physiology,"  1915,  1,  p.  1. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING     469 

On  the  basis  of  work  on  a  diabetic  and  comatose  boy  weigh- 
ing 32  kg.,  Magnus-Levy1  makes  the  following  computation  of 
metabolism.  He  purposely  assumes  a  high  requirement  of 
energy  for  a  lad  of  this  size,  or  50  to  55  calories  per  kilogram, 
which  calls  for  a  total  of  1600  to  1700  calories.  The  boy 
burned  90  grams  of  protein  and  perhaps  200  grams  of  fat: 

Calories. 
90  grams  protein  =     369  calories)  _         _ 

200  grams  fat  =  1909  calories] ' '  ~   22' 

Deduct  97.5  grams  oxybutyric  acid,  443  calories) 

=     628 

Deduct  50  grams  urinary  sugar,  185  calories..  .  J 

Calories  available 1650 

Here  we  perceive  an  extreme  case  of  diabetic  metabolism 
in  which  half  the  energy  contained  in  protein  is  excreted  in 
urinary  sugar  and  20  per  cent,  of  that  contained  in  fat  is 
eliminated  in  the  unburned  /3-oxybutyric  acid. 

This,  then,  is  the  worst  picture  of  the  perverted  metabolism 
in  diabetes.  Sugar  cannot  burn,  fat  burns  only  as  far  as 
/3-oxybutyric  acid,  and  as  for  protein,  a  part  of  its  amino-acids 
are  converted  into  sugar  and  another  part  into  /3-oxybutyric 
acid,  neither  of  which  can  be  burned. 

It  is  notable  that  the  phlorhizinized  cancer  patient  of 
Stanley  Benedict  (see  p.  455)  who  had  a  D  :  N  ratio  of  3.66 
excreted  37  grams  of  /3-oxybutyric  acid  and  4  grams  of  am- 
monia daily,  which  shows  that  the  acidosis  of  diabetes  is  co- 
incident with  a  lack  of  sugar  oxidation.  In  the  diabetic  C.  K. 
(see  p.  478)  a  fall  in  the  /3-oxy  butyric  acid  excretion  preceded 
the  break  in  the  D  :  N  ratio  (consult  p.  271). 

Von  Noorden2  and  Magnus-Levy3  report  cases  in  which 
there  was  a  considerable  excretion  of  aceton  bodies  in  the 
urine  when  carbohydrates  were  burned.  For  example,  one 
patient  eliminated  4.9  grams  of  /3-oxybutyric  acid  on  a  day 
when  40  grams  of  starch  were  ingested  and  burned.     There 

1  Magnus-Levy:  "Ergebnisse  d.  inn.  Med.,"  1908,  i,  385. 

2  von  Noorden:   "Pathologie  des  Stoffwechsels,"  1907,  ii,  77. 
8  Magnus-Levy:    "Ergebnisse  d.  inn.  Med.,"  1908,  i,  404. 


470  SCIENCE   OF   NUTRITION 

are  great  individual  variations.  Thus,  Staubli1  reports  con- 
cerning a  diabetic  man  whose  ordinary  mixed  diet  was 
changed  to  one  of  meat  and  fat,  including  50  grams  of  bread, 
the  whole  containing  3200  calories.  After  ten  days  of  this 
diet,  during  which  the  sugar  output  remained  nearly  constant 
at  100  grams,  the  /3-oxybutyric  acid  fell  from  37.5  grams  daily 
to  nothing.  In  commenting  on  his  results  Staubli  says: 
"The  important  factor  which  causes  a  more  serious  condition 
in  the  metabolism  of  a  diabetic  is  the  quantity  in  which  carbo- 
hydrate is  administered  in  excess  of  the  tolerance  for  sugar. 
Damage  caused  by  a  continual  overworking  of  the  sugar- 
burning  capacity  plays  a  large  part  in  the  progress  of  the  dis- 
ease. The  considerable  withdrawal  of  carbohydrates  from 
the  diet,  even  in  cases  of  severe  diabetes  with  high  acidosis, 
exerts  an  extraordinarily  beneficial  influence.  This  can  be  in 
part  explained  by  the  increased  ability  to  burn  sugar  on  ac- 
count of  the  conservation  of  the  body's  power  in  this  direction. 
The  improvement  in  the  capacity  for  sugar  combustion  ex- 
erts on  its  side  a  beneficial  action  on  the  acidosis." 

Turning  the  attention  now  to  the  character  of  the  total 
metabolism,  one  finds  that  the  severely  diabetic  patient  lives 
at  the  expense  of  protein  and  fat,  both  of  which  are  incom- 
pletely oxidized  by  his  organism.  It  follows  that  the  ordinary 
methods  of  computation  of  the  respiratory  quotients  and  of 
the  heat  value  of  the  protein  and  fat  metabolism  must  be 
scrutinized. 

Magnus-Levy2  was  the  first  to  make  calculations  of  this 

sort.     Lusk3  has  reviewed  the  subject  and  has  published  a 

calculation  for  the  value  of  the  respiratory  quotient  of  protein 

when  the  urinary  D  :  N  ratio  is  3.65: 

02.  co>. 

Grams.  Grams. 
Normal   oxidation   of    100   grams   beef 

protein 13S.18  152.17 

Deduction  for  16.28  gm.  X  3.65  which 

corresponds  to  59.41  gm.  glucose 63.38  87.15 

74.80  65.02 

1  Staubli:    "Deutsch.  Arch.  f.  klin.  Med.,"  1908,  xciii,  125. 

2  Magnus-Levy :    "Archiv  fur  Physiologic"  1904,  379. 

3  Lusk:    "Archives  of  Internal  Medicine,"  1915,  xv,  939. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING     47 1 

Converting  the  ratio  of  weights  into  the  ratio  of  volumes 
one  finds  that  the  diabetic  R.  Q.  for  protein  is  0.632. 

The  following  calculation  shows  the  caloric  value  to  the 
organism  of  1  gram  of  urinary  nitrogen  in  diabetes  when  the 
D  :N  is  3.65: 

Calories. 

Normal  value  of  1  gm.  urinary  N 26.51 

Deduct  glucose  3.65  X  3.692  calories 13.47 

Value  of  1  gm.  urinary  N  in  diabetes 13.04 

If  large  amounts  of  ammonia  are  eliminated  without  being 
synthesized  to  urea — which  is  produced  by  an  endothermic 
reaction — i  calorie  per  gram  of  such  extra  ammonia  nitrogen 
may  be  added  to  the  calculated  heat  production. 

If  one  uses  the  modified  figures  to  calculate  the  "non- 
protein respiratory  quotient"  in  severe  diabetes,  it  is  found 
that  the  combustion  of  fat  is  indicated.  A  few  illustrative 
calculations  are  given  below,  taken  from  the  work  of  Lusk  and 
of  Allen  and  DuBois: 

Non-protein 
D  :  N.  R.  Q.  R.  Q. 

Phlorhizinized  dog -  3.54  0.687  0.704 

Diabetic  man  (G.  S.) 3.5  0.697  0.700 

Diabetic  man  (C.  K.) 3.97  0.687  0.699 

The  last  subject  eliminated  71  grams  of  /3-oxybutyric  acid 
on  the  day  of  the  experiment.  It  is  evident  that  when  allow- 
ance is  made  in  the  calculations  for  the  altered  course  of  the 
metabolism  of  protein  in  diabetes,  the  remainder  of  oxidizable 
substance  possesses  approximately  the  respiratory  quotient  of 
fat,  which  is  0.707. 

Theoretically  speaking,  the  subject  is  more  complicated. 
For  example,  if  ammonia  be  used  to  neutralize  /3-oxybutyric 
acid,  the  carbon  dioxid  with  which  it  would  have  united  to 
form  urea  will  be  eliminated  in  the  respiration  and  tend  to 
raise  the  respiratory  quotient. 

Magnus-Levy  has  called  attention  to  a  possible  reduction 
in  the  respiratory  quotient  when  j8-oxybutyric  acid  is  formed 
from  fat.     He  estimates  that  the  maximal  quantity  of  /?-oxy- 


47 2  SCIENCE   OF   NUTRITION 

butyric  acid  derivable  from  ioo  grams  of  fat  is  36  grams. 
Under  these  circumstances,  the  respiratory  quotient  for  fat 
would  be  reduced  from  0.707  to  0.669.  The  case  is  not  so 
simple,  however,  for  if  the  36  grams  of  acid  formed  neutralized 
sodium  bicarbonate,  15.23  grams  of  carbon  dioxid  would  be 
eliminated. 

These  relations  are  shown  in  the  following  table: 

THEORETIC    RESPIRATORY    QUOTIENT    WITH  /J-OXYBUTYRIC 
ACID    FORMED    FROM    FAT 

Oxygen,       Carbon  Dioxid, 

Liters.                  Liters.  R.  Q. 

100  gm.  fat 201.9                142.73  0.707 

36  gm.  /3-oxybutyricacid.     34.85               30.96  0.889 

167.05  ni-77  0.669 

Add   for    15.23    gm.    C02 

fromNaHCOs 7.74 

Possible  end-result 167.05  iiQ-5*  °-7i5 

Since  other  bases  than  sodium  bicarbonate  may  be  used  for 
the  neutralization  of  /3-oxybutyric  acid,  it  is  apparent  that 
the  exact  determination  of  the  theoretic  respiratory  quotient 
when  this  acid  is  produced  in  large  amounts  in  human  diabetes 
is  at  present  impossible. 

The  establishment  of  the  diabetic  quotient  at  the  level  of 
0.69  also  throws  light  on  the  dogma  regarding  the  conversion 
of  fat  into  sugar.  Pembrey1  calculated  that  if  olein  were  in 
large  part  converted  into  glucose  the  respiratory  quotient  for 
the  reaction  would  be  0.281.  The  actual  findings  of  the  res- 
piration measurements  carry  the  refutation  of  the  idea  that 
fat  may  be  converted  into  sugar. 

It  may  be  well  to  insert  a  warning  against  the  too  literal 
interpretation  of  respiratory  quotients  obtained  under  grossly 
abnormal  circumstances.  This  may  be  illustrated  by  the  ex- 
periments of  Porges  and  Salomon,2  who  ligated  the  abdominal 
aorta  and  the  inferior  vena  cava  just  below  the  diaphragm  in 
depancreatized  dogs,  thereby  cutting  off  the  blood-supply  to 
the  abdominal  organs  and  probably  eliminating  half  the  normal 

1  Pembrey:    "Journal  of  Physiology,"  1901-02,  xxvii,  71. 

2  Porges  and  Salomon:   "Biochemische  Zeitschrift,"  1910,  xxvii,  143. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING    473 

quantity  of  blood  from  the  circulation.  Under  these  circum- 
stances the  respiratory  quotient  rose  to  unity  and  the  authors 
concluded  that  the  diabetic  organism  could  oxidize  glucose. 
This  doctrine  was  refuted  by  Murlin,  Edelmann,  and  Kramer,1 
who  showed  that  the  high  respiratory  quotient  was  merely 
incident  to  the  elimination  of  carbon  dioxid  from  the  blood 
itself. 

One  by  one  the  bulwarks  of  the  doctrine  of  the  conversion 
of  fat  into  glucose  have  been  shattered,  and  it  may  now  be 
relegated  to  the  realm  of  scientific  superstition. 

Among  the  earliest  investigations  of  Pettenkofer  and  Voit2 
was  a  respiration  experiment  on  a  diabetic  individual.  The 
authors  compared  the  metabolism  of  a  diabetic  with  that  of  a 
normal  man,  as  indicated  in  the  following  table: 

COMPARISON  OF  A  NORMAL  AND   A   DIABETIC  MAN 

Grams.  Grams  Burned 

in  the  Food.  in  the  Body. 

Healthy  man,  Protein 120  120 

"      Fat 112  83 

_  "     _      "      Sugar 344  344 

Diabetic  man,  Protein 107  158 

"      Fat 108  158 

"      Sugar.  ...-. ,  ._ 337  o 

(337  grams  of  sugar  in  the  urine.) 

It  is  seen  here  that  the  fat  and  protein  metabolism  are  in- 
creased in  order  to  compensate  for  the  non-combustion  of  the 
sugar.  Several  years  later,  on  the  basis  of  these  experiments, 
E.  Voit  calculated  that  a  diabetic  on  a  moderate  mixed  diet 
yielded  1015  calories  per  square  meter  of  surface,  while  the 
normal  individual  of  similar  build  produced  1020  calories. 

The  diabetic  condition,  therefore,  does  not  involve  a  de- 
crease in  the  quantity  of  energy  produced,  but  only  an  altera- 
tion in  the  source  of  the  energy. 

In  iqio  DuBois  and  Veeder3  published  experiments  ac- 
complished with  Pettenkofer- Voit  respiration  apparatus  in 
Kraus's  clinic  at  Berlin,  which  showed  that  a  diabetic  patient 

1  Murlin,  Edelmann,  and  Kramer:  "Journal  of  Biological  Chemistry," 
1913-14,  xvi,  70. 

2  Pettenkofer  and  Voit:    "Zeitschrift  fur  Biologie,"  1867,  iii,  380. 

3  DuBois  and  Veeder:    "Archives  of  Internal  Medicine,"  iqio,  v,  37. 


474  SCIENCE    OF    NUTRITION 

produced  5  per  cent,  more  heat  than  a  normal  man  of  the  same 
size,  the  food  intake  and  the  amount  of  muscular  activity  being 
the  same  in  both. 

Rubner1  found  the  metabolism  of  a  fasting  dog  was  the 
equivalent  of  477.8  calories  per  day,  which  rose  to  510.4 
calories  after  the  administration  of  phlorhizin,  an  increase  of 
7  per  cent.  This  increase  Rubner  rightly  attributed  to  the 
specific  dynamic  action  of  the  increased  protein  metabolism. 
Lusk2  has  reported  an  increase  in  the  heat  production  of  70 
per  cent,  after  administering  phlorhizin  to  a  dog. 

The  same  influences  are  active  in  the  depancreatized  dog, 
the  heat  production  being  increased  42  per  cent.,  according  to 
Falta,  Grote  and  Staehelin,  and  Murlin  and  Kramer.3 

In  the  phlorhizinized  man  of  Stanley  Benedict  (see  p.  455) 
the  protein  metabolism  did  not  increase  as  happens  in  other 
species,  and  it  is  therefore  open  to  question  whether  there  was 
any  increase  in  his  total  energy  production. 

The  question  of  the  total  energy  production  in  the  human 
diabetic  has  been  extensively  studied  by  Benedict  and  Joslin4 
and  by  Allen  and  DuBois.5  Whatever  of  criticism  may  be 
found  in  the  following  lines,  it  is  to  be  borne  in  mind  that  there 
is  no  question  of  the  absolute  accuracy  of  all  of  this  work;  the 
criticism  only  regards  the  interpretation.  Pfliiger  has  truly 
stated  that  criticism  is  the  mainspring  of  every  advance  and 
the  Altmeister  added,  "deshalb  iibe  ich  es." 

Lusk6  criticized  the  first  publication  of  Benedict  and 
Joslin  and  computed  that  the  average  increase  in  metabolism 
was  not  15  per  cent,  above  the  normal,  as  was  stated,  but  did 
not  exceed  5  per  cent.  The  second  publication  of  Benedict 
and  Joslin  maintained  that  there  was  an  increase  of  between. 

1  Rubner:    "Gesetze  des  Energieverbrauchs,''  1902,  p.  370. 

2  Lusk:    "Journal  of  Biological  Chemistry,"  1915,  xx,  598. 

3  Falta,  Grote,  and  Staehelin:  "Hofmeister's  Beitrage,"  1907,  x,  199. 
Murlin  and  Kramer:    "Journal  of  Biological  Chemistry,"  1913,  xv,  380. 

4  Benedict,  F.  G.,  and  Joslin:  "Metabolism  in  Diabetes  Mellitus,"  1910; 
"Metabolism  in  Severe  Diabetes,"  191 2. 

5  Allen  and  DuBois:    "Archives  of  Internal  Medicine,"  1916,  xvii,  1010. 

6  Lusk:    "Science,"  1911,  xxxiii,  434. 


METABOLISM    IN   DIABETES    AND    PHOSPHORUS-POISONING     475 

15  and  20  per  cent,  in  patients  suffering  from  diabetes,  and 
attributed  the  increase  to  acidosis. 

The  establishment  of  an  accurate  method  of  determining 
the  basal  metabolism  of  normal  men  through  the  labors  of 
DuBois  has  given  a  method  of  interpretation  of  metabolism 
results  which  has  not  heretofore  been  available.  If  the  height- 
weight  chart  of  DuBois  be  used  to  obtain  the  surface  area  and 
be  applied  to  the  diabetic  cases  and  normal  controls  of  Bene- 
dict and  Joslin  ("Severe  Diabetes,"  Table  132),  the  following 
calculations  may  be  made  :l 

Per  Cent. 

Average  variation  from  normal  of  20  controls —8.6 

Average  variation  from  normal  of  19  diabetics +2.0 

The  increase  in  metabolism  is,  therefore,  2  per  cent, 
above  the  true  normal,  but  11  per  cent,  above  the  normal 
controls  selected  by  Benedict  and  Joslin.  This  selection 
may  have  been  justified,  for  in  order  to  choose  individuals  who 
were  like  the  diabetic  patients,  emaciated  controls  were  in- 
dicated and  such  show  a  subnormal  basal  metabolism.  Allen 
and  DuBois  have  pointed  out  that  herein  lies  the  fundamental 
cause  of  the  divergency  in  viewpoint.  These  authors  have 
published  a  summary  of  the  carefully  investigated  cases  of 
diabetes  mellitus,  26  in  all.  They  found  that  the  basal  metab- 
olisms of  one-half  of  these  were  within  the  normal  range  of 
±10  per  cent.;  9  cases  showed  increases  of  11  to  23  per  cent, 
above  the  normal  basal.  Of  these  cases  which  manifested  a 
higher  metabolism,  3  had  severe,  2  marked,  1  moderate,  and 
3  little  or  no  acidosis.  The  patient  who  showed  the  greatest 
rise  in  metabolism  had  very  slight  acidosis.  Four  patients 
showed  metabolisms  of  between  14  and  19  per  cent,  below 
the  normal.  Of  the  17  patients  whose  basal  metabolisms 
were  normal  or  below  the  normal,  8  manifested  very  severe 
acidosis.  The  conclusion  follows  that  acidosis  cannot  be 
the  immediate  cause  of  the  increased  metabolism  when  this 
is  found  in  diabetes. 

1  Allen  and  DuBois:    Loc.  cit. 


476 


SCIENCE   OF   NUTRITION 


In  their  analysis  Allen  and  DuBois  considered  for  the 
first  time  the  factor  of  emaciation.  They  call  attention  to 
Magnus-Levy's1  description  of  a  neurasthenic  youth  who  had 
partially  starved  himself  for  a  year  or  more.  On  entrance  to 
the  hospital  he  was  "skin  and  bones."  During  the  first 
experimental  period  he  was  given  his  former  dietary  containing 
700  to  800  calories  daily  and  was  then  given  abundant  food. 


Date. 


Nov.  16  to  21.  .  . 
Nov.  23  to  Dec.  9 
Mar.  13  to  May  8 


Weight 
in  Kg. 


36.2 
38.O 
52.2 


Calories 

per 

Hour. 


34-8 
44.9 
61.9 


Calories 

per 

Sq.  M. 

per  Hour. 


26.6 
33-0 
40.5 


Relationship  of 

Metabolism  to 

Average  Normal 

of  3Q.7. 


-33% 
-17% 
+   2% 


Remarks. 


Low  diet. 
Liberal  diet. 
Liberal  diet. 


These  valuable  data  indicate  that  if  a  man  whose  metab- 
olism is  normal  has  been  reduced  in  weight  by  30  per  cent., 
his  metabolism  when  he  is  fed  with  a  low  dietary  may  be 
reduced  44  per  cent,  below  the  actual  normal  level,  or  33  per 
cent,  below,  as  measured  by  the  normal  per  square  meter  of 
surface.  If  a  liberal  diet  be  given  at  this  juncture,  the  total 
heat  production  is  26  per  cent,  below  the  actual  normal,  or 
17  per  cent,  below  if  recorded  on  the  basis  of  surface  area. 
This  leads  to  the  query  whether  basal  metabolism  of  the 
emaciated  diabetic  is  not  really  below  that  of  a  normal  man. 

Among  the  cases  cited  by  Allen  and  DuBois  there  are  6 
who  show  an  emaciation  of  over  20  per  cent.,  as  follows: 


Case. 

Urinary  N  per  Day, 
Grams. 

Per  Cent.  Loss  from 

Greatest  Body 

Weight. 

Per  Cent.  Variation 

from  Normal  Calories 

per  Sq.  M. 

I 

14 
9-12 

7-  9-5 
20 
11-15 

14-20 

3° 
28 
26 
27 
31 
42 

+  14* 

T 

V 

+  15 
+  3 
-   5 

-is 

+  3 

C.  K 

G.  S 

W.  G. .  . 

Average 

*  Nervous  individual. 
1  Magnus-Levy:   "Zeitschrift  fur  klin.  Med.,"  1906,  lx,  177. 


METABOLISM   IN    DIABETES    AND    PHOSPHORUS-POISONING     477 


It  is  evident  that  if  the  metabolism  of  a  normal  man,  who 
through  emaciation  has  lost  30  per  cent,  of  his  body  weight, 
is  33  per  cent,  (or  when  well  nourished  17  per  cent.)  below  the 
normal  level  of  metabolism,  then  the  emaciated  diabetic  has  in 
reality  a  higher  heat  production  than  he  would  have  had  if  he 
had  been  free  from  diabetes.  This  is  emphatically  shown  in 
the  case  of  C.  K.,  soon  to  be  more  fully  described.  This  in- 
dividual, who  had  diabetes  in  a  severe  form,  subsequently 
became  entirely  free  from  sugar  and  manifested  a  high  degree 
of  tolerance  for  carbohydrate.  The  metabolism  of  the 
different  periods  may  thus  be  summarized : 


Condition. 


C.  K. 


Severe  diabetes . 
Severe  diabetes . 
Recovery 


Weight. 

Urine. 

R.  Q. 

Kg. 

N. 
Gm. 

56-7 
56.5 
45-3 

364 
20.0 

0.687 

0.707 

O.Q2 

Per  Cent.  Loss 
from  Greatest 
Body  Weight. 


Per  Cent. 

Variation 

from  Normal 

Calories  per 

Square  Meter 

of  Surface. 


27 
43 


+  15 
+  3 
-36 


It  is  evident  that  in  this  emaciated  individual  the  metab- 
olism would  have  been  lower  in  the  first  instance  had  he  not 
been  diabetic.  The  high  protein  metabolism  would  sufficiently 
account  for  the  increased  total  heat  production  in  this  patient, 
although  in  some  other  instances  of  increased  metabolism  in 
diabetes  this  factor  does  not  apparently  always  suffice  to 
explain  the  increase.  The  frequent  presence  of  lipemia 
(see  p.  252)  may  explain  in  part  the  increased  metabolism. 
The  onset  of  diabetes  in  this  case  was  very  rapid.  Nowhere 
in  the  literature  is  the  protein  metabolism  in  diabetes  men- 
tioned as  being  so  high,  and  in  no  other  case  are  the  results  of 
metabolism  experiments  so  nearly  akin  to  those  obtained  in 
experimental  animals. 

A  preliminary  report  of  the  patient  C.  K.  of  Geyelin  and 
DuBois1  gives  details  of  his  metabolism  in  a  table  which  is 
reproduced  on  page  478. 

1  Geyelin  and  DuBois:  "Journal  of  the  American  Medical  Association," 
1916,  kvi,  1532. 


478 


SCIENCE    OF   NUTRITION 


U 


Weight, 
Kg. 

f-»  r*oD  O   r-  i>-0  O   t>-0  r*-0  O   ->t  *t  <0  <"0        «nwm 

M00    fO 
M    1O00 

Average 
Calories 
per  So.  M. 
per  Hour, 
Linear 
Formula.' 

r^O     .CO     .  q     .  o>    .     .     . 

■  io  «    •  d    '  «*>  *  v>  '    ■ 

;  1A  0. 

Average 

Calories 

per 

Hour. 

CO*t.M.r^!.00 

"00    N      '   f.      "SO       "\C 

0  0 
■  it  »^ 

Average 

Non- 
protein. 
R.Q. 

O  «o     .  \o      .  CO      .  00      .      .      .           .... 

Ot     .O      -h      ,    w 

■   *   •    ,   *   ■  6  6    '  6    '  6    •  6 

0  O 

m 
o   . 

< 

CO   ►«     .   o     .   «     .   *o 

6  6      o    ■  6    •  6    • 

.  m  0 

'.  O-00 
O   0 

Blood 

Sugar, 

Per 

Cent. 

^    .   0   <n O     .nOh^o     .     .           .  *r> 

m.ti-m in     .  t^  r-cc   O      •      •           •   O 

ooo OOOOO'           o 

Blood 

Mm. 
Hg. 

rr    .€   h  N^     !    C>0   -t-tN^/     -CO   <*3N   o          .   o^     .      .           .      .      . 

Beta- 

OXYBU- 
TYRIC 

Acid, 
Gm. 

OO    N    ^NMlfl     ,       .       .              .    M       .       . 

r-«©     .  O  0  o  N  °5  M  "*>  ^oo  h  n  o    .     .     .          .  ■*    .     . 

to  **■     "   O   <*)  r^.  "".<  O   "">  r-co"  *0   m  o   O 

tj-  fo    *  o  »o  io  to  t^  t^co  m  u-;  -»t  r<  m     *                    ■  o 

:  0  0 

D  :N 
Ratio. 

oo   m   »/■)  r-        r^f^t^M   r^O   i^'twjM      •      •      •           .... 

•C  -C    C  >-  CO   CNOOOO  r*--o   *f>o   M     ■ 

:  0  0 

<N<N<NO)MMMfO'J-r'0C'IC>)C4NM 

Urine, 
N,  Gm. 

O>00  COO   wi-r-rON   (N   O   r-O   •■+  <n    't'ONN   w,  0   r*-  r-. 
r^.  O-  **  O   -3-  m  r-*vO  cO*   OO   't  "1"00   O  CO   n   *t  O   0<CO 

00   .  . 

hg 
?  o  «: 

Oo 

O^fN   O   O   r-  ir>  o,  *+  «   m   e*   fONOO   t-t   r-  -^ 

■4oo"  4co  (ncoco  r^fAd  iA^^o^n^m  d  o  o  ^-  -f- 

r-t^.r>-0  m   m   m<j  i^Tj-in^w)fO«   m  m   pom 

000 

a 
o 

< 

H 

§ 

o 

to 

r^Ow^MOsOO1                          *■*        COCO                     O 
O   O   O   r^  <>co   mmu-,  (mOOOOOO1^.  ^-OOOr^O 

M    O      IO    *0    ^                                                                                         MM 

0  : 

1 
FN 

m  m   <n        vo         Tt                                                                  O 

o  o  o  r-»  d  "".06  coddoooONoddoooHO 

m    to  iy,  10  m    O  f*5               m«m          CO>                     *>"> 

0    ! 

a*! 

u     ^ 

m                 ro^-t-t                 OOO 
OOO^-OO^^OOOOmmw-,  OOOOOOOO 

0    ! 

Date. 

0*  O  m  w  fo  ^t  100  1^-00  O'  0  n  n  to  «t  uvo  r^co  0  0  •■« 

1     w>     - 

c-p  a 

^  1     1     1     l     l     1     1     1     l     l     1     1     1     t     1     l     1     1     1     1     l     I     1 

M  CO   Q  O   m   *n   *rs  Tf  ino   r-cO   <>  0   *-"   m   iv)  -t  i/-.sc    r-cO    O  O 

(JUUUUUUUUUUUUUUUUUUUUUUO 

OQQQQOOOaOODODCOCQDOCQQ " 

METABOLISM    IN    DIABETES    AND    PHOSPHORUS-POISONING     479 

On  the  fifth  day  of  a  preliminary  fast  the  D  :  N  ratio  of 
this  man  was  2.95.  Then  for  four  days  he  was  given  a  mixed 
diet,  moderate  in  quantity.  After  this  followed  a  diet  con- 
taining about  100  grams  of  protein  and  the  D  :  N  rose  to  3.97, 
4.01,  and  3.87  on  three  successive  days.  On  the  first  of  these 
days  there  was  distinct  drowsiness;  there  were  36.4  grams  of 
nitrogen  in  the  urine  after  an  intake  of  19  grams  in  the  food; 
71  grams  of  /3-oxybutyric  acid  were  eliminated  in  the  urine 
or  about  the  quantity  which  could  have  arisen  from  the  oxi- 
dation of  fat  during  the  period;  the  carbonic  acid  tension  in 
the  blood  was  one-half  the  normal,  and  the  respiratory  quotient 
was  0.687.  The  metabolism  presented  the  picture  of  com- 
plete diabetes  (see  p.  469).  Several  who  saw  the  patient 
pronounced  the  outlook  hopeless.  Joslin,  who  happened  to 
be  in  New  York  at  the  time,  gave  a  favorable  prognosis. 
This  prognosis  was  correct.  A  period  of  fasting  interrupted 
by  days  of  very  low  diets  resulted  in  the  complete  disappear- 
ance of  glucose  and  of  high  nitrogen  elimination  in  the  urine 
within  ten  days,  and  on  the  eleventh  day  only  0.2  gram  of 
/3-oxybutyric  acid  was  eliminated. 

Joslin  has  for  a  long  time  privately  informed  the  writer 
that  he  would  not  place  a  patient  upon  a  diet  consisting  of 
protein  and  fat  alone  on  account  of  the  deleterious  effects  which 
might  be  produced,  and  he  has  stated  in  personal  conversation 
that  fatal  results  might  ensue  if  the  diet  were  long  continued. 
The  experiment  on  C.  K.  as  well  as  one  unpublished  experi- 
ment not  here  described  show  most  clearly  that  Joslin  is  cor- 
rect as  regards  the  evil  effect  of  even  a  moderately  high 
protein  intake  upon  the  diabetic  patient. 

The  case  of  C.  K.  exemplifies  the  method  of  modern 
treatment  of  diabetes  known  as  the  "Allen  method."  Wein- 
traud,1  in  the  clinic  of  Naunyn,  was  the  first  to  recommend  the 
interpolation  of  occasional  fasting  days  for  the  benefit  of  the 
diabetic  patient,  and  Naunyn2  practised  the  reduction  of  the 

1  Weintraud:    "Centralbla't  fiir  klinische  Medizin,"  1893,  xiv,  737. 
*  Naunyn:    "Zeitschrift  fiir  arztliche  Fortbildung,"  1908,  v,  737. 


480  SCIENCE    OF   NUTRITION 

body  weight  of  the  patient,  both  by  interposing  single  fasting 
days  and  by  giving  600  grams  of  green  vegetables  which  con- 
tain little  nourishment.  Allen,  however,  on  the  basis  of 
many  fasting  experiments  with  depancreatized  dogs,1  ob- 
tained information  which  he  was  subsequently  able  to  apply  to 
many  diabetic  patients2  in  the  Rockefeller  Hospital.  It  is 
certain  that  he  was  the  first  to  introduce  a  rigorous  regime  of 
fasting  until  the  diabetic  patient  becomes  free  from  urinary 
glucose  and  from  acidosis.  Frequently  whisky  was  admin- 
istered as  the  only  nourishment.  Benedict  and  Torok3  were 
able  to  reduce  the  aceton  excretion,  as  well  as  that  of  nitrogen 
and  glucose,  after  administering  alcohol  to  a  diabetic.  The 
experiments  of  Otto  Neubauer4  showed  that  red  wine  reduced 
the  sugar  output  and  the  acidosis  in  diabetes,  and  Allen  and  Du- 
Bois  find  indications  that  the  administration  of  whisky  favors 
the  oxidation  of  glucose  in  the  diabetic.  Joslin5  and  Allen  and 
DuBois  report  that  during  the  clearing  up  of  the  diabetes  in  a 
fasting  patient  respiratory  quotients  are  found  which  are 
higher  than  could  possibly  be  obtained  from  the  oxidation  of 
body  protein  and  fat  alone.  This  may  possibly  be  due  to  the 
oxidation  of  the  accumulated  aceton  bodies,  the  respiratory 
quotient  of  /3-oxybutyric  acid  being  0.89,  an  explanation 
given  by  Joslin,  who  has  found  respiratory  quotients  in  fasting 
diabetics  as  high  as  0.8. 

Although  the  great  majority  of  diabetic  patients  are 
cured  by  the  fasting  treatment,  so  that  they  may  live  on  a 
carefully  regulated  diet  without  showing  glycosuria,  still 
there  are  some  cases  that  do  not  yield  to  such  treatment. 
Joslin6  has  reported  concerning  14  such  patients  who  were 
diabetics  of  long  standing,  or  very  severe  or  complicated 
cases. 

1  Allen:    "Glycosuria  and  Diabetes,"  Boston,  1913. 

2  Allen:  "Journal  of  the  Amer.  Med.  Assoc,"  1914,  lxiii,  939;  Ibid.,  1916, 
lxvi,  1525. 

5  Benedict  and  Torok:   "Zeitschrift  fur  klinische  Medizin,"  1906,  lx,  329. 
4  Neubauer,  O.:    "Miinchener  med.  Wochenschrift,"  1906,  liii,  791. 

3  Joslin:   "American  Journal  of  the  Medical  Sciences,"  191 5,  cl,  485. 

6  Joslin:  "Boston  Medical  and  Surgical  Journal,"  1916,  xlxxiv,  371  and  425. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING     481 


One  of  the  most  interesting  researches  upon  diabetes  ever 
accomplished  is  that  of  H.  O.  Mosenthal  in  Janeway's  Balti- 
more clinic.  At  this  writing  the  results  have  not  been  pub- 
lished, but  are  presented  here  by  special  permission. 

The  following  table  shows  the  results  obtained  from  a 
fasting  diabetic  with  a  D  :  N  ratio  closely  approximating  that 
found  in  the  phlorhizinized  dog,  and  resembling  a  phlorhizin- 
ized  man  (see  p.  455)  both  as  regards  the  D  :  N  ratio  and  in 
the  quantities  of  ammonia  and  /3-oxybutyric  acid  eliminated. 

DIABETIC   PATIENT  PRACTICALLY  FASTING 

(One  egg  and  green  vegetables  containing  2  to  6  grams  carbohydrate  per  day 
during  last  five  days.  Wh.  =  whisky;  Wi.  =  wine.  Bicarbonate  of  soda  also 
administered.    The  D  :  N  is  calculated  after  subtracting  ingested  carbohydrate.) 


Day  of 
Fast. 

Glucose. 

Nitro- 
gen. 

D  :N. 

/3-OxYBU- 

tyric  Acid. 

NH3-N. 

Alveolar 

COo 
Tension. 

Alcoholic 
Beverage. 

4 

5 

6 

7 

8 

9 

10 

11 

12 

13 

Grams. 

30-9 
40.3 
36.3 
31-9 
35-1 
38.O 

34-7 
35-7 

Death. 

Grams. 

10.2 

10.8 

9.8 

9.0 

9.6 

10.5 

8.9 

8-7 

3-64 
3-/I 
340 
2.89 
3-44 
3.28 
3-58" 
3.68 

Grams. 
64.9 
66.0 
50.6 
64.9 
78.0 
ill. 2 
106.6 
73-o 

Grams. 

4-3 
4-5 
4.2 

3-9 
4.4 

4-4 
4.0 
4.2 

Mm. 
19-5 

24.6 

c.c. 

40  Wh. 

24  Wh. 
8  Wh.* 
490  Wi. 
345  Wi. 

*  And  360  c.c.  wine. 

At  the  beginning  of  the  investigation  the  blood  sugar  of 
the  diabetic  was  0.33  per  cent.,  but  fell  on  the  eighth  and  ninth 
days  to  0.25  and  0.24  per  cent. 

The  advent  of  the  Allen  fasting  treatment  seemed  at  first 
likely  to  make  it  possible  to  dispense  with  laboratory  records 
concerning  diabetic  cases,  but  it  is  still  necessary  in  10  per 
cent,  and  perhaps  more  of  the  cases  to  follow  the  sugar  output, 
and  the  intensity  of  the  acidosis  for  these  do  not  invariably 
diminish. 

Joslin's  method2  of  applying  the  Allen  treatment  is  here 
reproduced : 

2  Consult  Joslin:  "The  Treatment  of  Diabetes  Mellitus,"  1916,  p.  243. 


482  SCIENCE    OF   NUTRITION 

Joslin's  Summary  of  Treatment 

Fasting. — Fast  until  sugar  free.  Drink  water  freely  and 
tea,  coffee,  and  clear  meat  broth  as  desired.  In  very  severe, 
long-standing  and  complicated  cases,  without  otherwise  changing 
habits  or  diet,  omit  fat,  after  two  days  omit  protein,  and  halve 
carbohydrate  daily  to  10  grams,  then  fast. 

Carbohydrate  Tolerance.— When  the  twenty-four-hour  urine 
is  sugar  free,  add  150  grams  of  vegetables  containing  5  per 
cent,  of  carbohydrate  and  continue  to  add  5  grams  carbohy- 
drates daily  up  to  20,  and  then  5  grams  every  other  day, 
passing  successively  upward  through  vegetables  containing  5, 
10,  and  15  per  cent,  of  carbodydrate,  fruits  containing  5  and 
10  per  cent,  of  carbohydrate,  potato  and  oatmeal  to  bread, 
unless  sugar  appears  or  the  tolerance  reaches  3  grams  carbo- 
hydrate per  kilogram  body  weight. 

Protein  Tolerance. — When  the  urine  has  been  sugar  free 
for  two  days,  add  20  grams  protein  (3  eggs)  and  thereafter 
15  grams  protein  daily  in  the  form  of  meat  until  the  patient  is 
receiving  1  gram  protein  per  kilogram  body  weight,  or  if  the 
carbohydrate  tolerance  is  zero,  only  f  gram  per  kilogram  body 
weight. 

Fat  Tolerance. — While  testing  the  protein  tolerance,  a 
small  quantity  of  fat  is  included  in  the  eggs  and  meat  given. 
Add  no  more  fat  until  the  protein  reaches  1  gram  per  kilogram 
(unless  the  protein  tolerance  is  below  this  figure),  but  then 
add  25  grams  daily  until  the  patient  ceases  to  lose  weight  or 
receives  not  over  40  calories  per  kilogram  body  weight. 

Reappearance  of  Sugar. — The  return  of  sugar  demands 
fasting  for  twenty-four  hours  or  until  sugar  free.  The  diet  is 
then  increased  twice  as  rapidly  as  before,  but  the  carbohydrate 
should  exceed  half  the  former  tolerance  until  the  urine  has 
been  sugar  free  for  two  weeks,  and  it  should  not  then  be  in- 
creased more  than  5  grams  per  week. 

Weekly  Fast  Days. — Whenever  the  tolerance  is  less  than  20 
grams  carbohydrate,  fasting  should  be  practised  one  day  in 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING    483 

seven;  when  the  tolerance  is  between  20  and  50  grams  carbo- 
hydrate upon  the  weekly  fast  day,  vegetables  containing  5  per 
cent,  carbohydrate  and  one-half  the  usual  quantity  of  protein 
and  fat  are  allowed;  when  the  tolerance  is  between  50  and  100 
grams  carbohydrate  the  10  and  15  per  cent,  vegetables  are 
added  as  well.  If  the  tolerance  is  more  than  100  grams  car- 
bohydrate, upon  weekly  fast  days  the  carbohydrate  should  be 
halved. 

Joslin1  writes,  "The  advantages  of  the  new  treatment  are 
many.  It  has  made  attainable  the  ideals  of  treatment, 
namely,  a  sugar-free  and  acid-free  urine.  The  standards  of 
the  success  of  treatment  are  so  simple  that  they  are  within  the 
reach  of  the  patient.  At  one  stroke  the  patient  is  delivered 
from  medicines,  patent  or  otherwise,  sham  kinds  of  treatment, 
gluten  breads,  and  in  ninety-nine  cases  out  of  a  hundred,  of 
alkalies."  With  his  increased  knowledge  Joslin2  does  not 
hesitate  to  carry  pregnancy  in  the  diabetic  to  term. 

Joslin  found  that  the  ingestion  of  fructose  by  a  diabetic 
did  not  increase  the  respiratory  quotient  (see  p.  296). 

Von  Noorden's  oatmeal  cure  has  occupied  a  prominent 
place  in  diabetic  therapy.  Blum3  denied  its  specific  efficacy 
and  attributed  the  results  to  the  low  protein  dietary.  Roily,4 
on  the  basis  of  respiratory  experiments,  concluded  that  there 
was  no  difference  in  the  value  of  the  various  forms  of  starch 
ingested  by  the  diabetic,  and  Joslin5  showed  the  failure  of 
either  oatmeal  or  potato  starch  to  raise  the  respiratory 
quotient  in  severe  diabetes.  Allen  believes  that  the  sig- 
nificance of  the  oatmeal  treatment  lies  in  the  fact  that  it  is 
usually  administered  after  interpolation  of  days  of  green 
vegetable  diets,  which  constitute  virtual  starvation,  while 
Joslin  states  that  in  the  salt  content  of  the  oatmeal  lies  its 
only  benefit.     Baumgarten  and  Grund6  have  separated  the 


1  Joslin 

2  Joslin 

3  Blum 

4  Roily 
1  Joslin 


"American  Journal  of  the  Medical  Sciences,"  1915,  cl,  489. 
"Boston  Medical  and  Surgical  Journal,"  1915,  clxxiii,  841, 
"Miinchener  med.  Wochenschrift,"  191 1,  lviii,  1433. 
"Deutsches  Archiv  fur  klin.  Med.,"  191 2,  cv,  494. 
'Archives  of  Internal  Medicine,"  1915,  xvi,  693. 


6  Baumgarten  and  Grund:  "Deutsches  Archiv  fur  klin.  Med.,"  1911,  civ,  168. 


484  SCIENCE   OF   NUTRITION 

starch  and  other  constituents  of  oatmeal  and  have  administered 
them  separately  to  diabetics  without  improving  their  condi- 
tion. 

The  elimination  of  /3-oxybutyric  acid  from  the  system  is 
furthered  by  the  administration  of  alkalies.  Staubli  reports  a 
diabetic  who  eliminated  34  grams  of  /3-oxybutyric  acid  daily 
when  the  diet  contained  60  grams  of  sodium  bicarbonate. 
This  excretion  fell  to  17  grams  on  a  diet  which  was  free  from 
alkali,  and  then  rose  to  45.2  grams  on  return  to  60  grams  of 
bicarbonate.  Such  treatment  with  alkali  is  sometimes  highly 
beneficial,  for,  as  Magnus-Levy  observes,  the  diabetic  does 
not  die  in  coma  because  of  the  neutralized  acid  which  is  elimi- 
nated in  the  urine,  but  rather  on  account  of  that  which  is 
retained  in  the  body  which  neutralizes  the  alkalies  of  tissue  and 
of  body  fluids. 

Von  Noorden1  reports  cases  of  diabetics  who  have  ex- 
creted 5  to  6  grams  of  aceton  and  30  to  40  grams  of  /3-oxy- 
butyric acid  in  a  day,  and  yet  have  lived  comfortably  for 
years. 

Alkali  therapy  has  long  been  considered  important  in 
the  treatment  of  diabetes.  Bicarbonate  of  soda  up  to  200 
grams  daily  has  been  given.  Weiland2  cites  a  case  in  which 
green  vegetables,  200  grams  of  meat,  and  1 20  grams  of  sodium 
bicarbonate  were  given  daily,  under  which  circumstances  the 
urine  contained  the  following  ingredients: 

Day. 

1234 

Aceton 14-4  "-8  I5-1  *3-i 

/3-oxybutyric  acid 90.8  68.4  105.9  90.7 

Glucose 138.9  132.0         i97-o  89.6 

Nitrogen 19.3  15.0  25.0  15.2 

Ammonia 1.3  1.1  2.9  1.9 

It  is  evident  that,  despite  the  high  acidosis,  the  ammonia 
is  kept  at  a  low  level  on  account  of  the  large  amount  of  alkali 
administered. 

1  von  Noorden:   von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1904, 

">  253- 

2  Weiland:   "Zeitschrift  fur  ex.  Path,  und  Ther.,     191 2-13,  xn,  116. 


METABOLISM   IN   DIABETES   AND   PHOSPHORUS-POISONING     485 

Murlin1  has  obtained  results  which  indicate  that  if  de- 
pancreatized  dogs  be  given  alkali  they  are  able  to  oxidize  some 
glucose.  This  accords  with  the  idea  that  diabetes  is  the 
result  of  acidosis  (see  p.  261).  Whether  alkali  therapy,  if 
applied  still  more  rigorously  than  heretofore  practised,  will 
enable  the  diabetic  patient  to  oxidize  glucose  is  a  question 
raised  by  these  experiments.2 

Nothing  except  dieting  affords  permanent  relief  in  dia- 
betes. Opium  is  said  to  reduce  the  sugar  output  in  cases 
bordering  on  the  severe  type.3  The  cause  of  this  action  is 
unknown.  Experiments  inaugurated  upon  an  individual 
having  the  3.65  :  1  ratio  might  indicate  whether  its  effect  was 
really  to  increase  the  combustion  of  sugar  or  only  to  reduce  the 
general  metabolism.  The  ingestion  of  extracts  of  different 
organs  does  not  apparently  influence  the  sugar  excretion. 
Laboratory  investigations  of  the  glycolytic  power  of  pancreas 
extracts  have  been  very  numerous,  but  have  failed  to  give 
striking  results.  It  is  possible  that  the  supposed  enzyme  or 
activating  substance  is  extremely  sensitive  to  a  change  in 
normal  conditions.  Mandel  and  Lusk  gave  large  quantities 
of  yeast  to  a  diabetic  man  without  changing  the  D  :  N  :  :  3.65  : 
1,  which  shows  that  the  enzymes  of  yeast  are  not  able  to 
penetrate  the  intestinal  wall  so  that  they  may  replace  the 
natural  ferment  of  the  organism. 

Raulston  and  Woodyatt4  made  an  intravenous  trans- 
fusion of  blood  from  a  normal  man  into  a  diabetic  individual, 
with  aggravation  of  all  the  symptoms  in  the  latter. 

Minkowski5  discovered  that  fructose  largely  reduced 
protein  metabolism  in  the  case  of  depancreatized  dogs.  This 
led  to  the  wide-spread  use  of  fructose  in  diabetes.  Mandel 
and  Lusk,  however,  found  that  the  increase  of  sugar  in  the 
urine  of  their  diabetic  man,  after  giving  100  grams  of  fructose, 

1  Murlin  and  B.  Kramer:  "Journal  of  Biological  Chemistry  "  1916,  xxvii,  517. 

2  Murlin:  Ibid.,  1016-17,  xxviii,  289. 

3  von  Noorden:    "Diabetes,"  1905,  p.  158. 

4  Raulston  and  Woodyatt:  "Journal  of  the  Amer.  Med.  Assoc.,"  1914,  Ixii, 
996. 

5  Minkowski:    Loc.  cil.,  p.  131. 


486  SCIENCE    OF   NUTRITION 

was  80  per  cent,  of  the  sugar  ingested.  The  fructose  had  no 
effect  whatever  on  protein  metabolism. 

Von  Noorden1  confirms  this  observation.  He  believes 
that  fructose  is  normally  produced  in  metabolism  and  is 
normally  burned.  In  very  rare  cases,  called  levulosuria, 
fructose  alone  appears  in  the  urine.  One  case  of  complete 
intolerance  for  fructose  has  been  reported.2 

The  negative  results  as  regards  the  value  of  fructose  were 
especially  interesting  in  the  case  of  Mandel  and  Lusk.  This 
diabetic  medical  student  was  confident  of  the  efficacy  of  fruc- 
tose on  account  of  opinions  expressed  by  the  writer  in  his  lec- 
tures. On  the  days  of  fructose  ingestion  the  patient's  spirits 
revived,  his  strength,  measured  on  the  ergograph,  decidedly 
improved,  and  his  companions  remarked  upon  the  benefit  re- 
ceived, all  of  which  shows  that  subjective  sensations  are  not 
to  be  used  as  scientific  criteria.  Staubli3  states  that  adminis- 
tration of  fructose  reduces  the  diabetic's  tolerance  for  glucose. 

In  this  connection  it  may  be  mentioned  that  ^-glucuronic 
acid  and  pentoses  have  a  bearing  on  carbohydrate  metabolism. 
A  large  variety  of  substances  (camphor,  chloral,  turpentine) 
form  syntheses  with  glucuronic  acid  in  the  organism,  and 
corresponding  glucuronates  are  then  eliminated  in  the  urine. 
At  first  glance  glucuronic  acid  appears  to  be  the  preliminary 
oxidation  product  of  glucose,  as  is  suggested  by  the  following 
equation : 

OCH(CHOH)4CH2OH     +     02     =     OHC(CHOH)4COOH     +     H-.0 

Glucose.  Glucuronic  acid. 

However,  Mandel  and  Jackson4  administered  camphor  to 
fasting  dogs  for  several  days  and  noted  the  excretion  of  glucu- 
ronic acid.  On  giving  large  quantities  of  glucose  the  protein 
metabolism  fell  and  with  it  the  glucuronic  acid  elimination; 
and  on  giving  the   animal  chopped   meat   the  quantity  of 

1  von  Noorden:    Loc.  cit.,  p.  50. 

2Neubauer:    "Munchener  med.  Wochenschrift,"  1005,  Hi,  1525. 

3  Staubli:   "Deutsches  Archiv  fiir  klin.  Med.,"  1908.  xciii,  125. 

4  Mandel  and  Jackson:  "American  Journal  of  Physiology,"  1902,  viii. 
Proceedings  of  the  American  Physiological  Society,  p.  xiii. 


METABOLISM   IN  DIABETES   AND   PHOSPHORUS-POISONING    487 

campho-glucuronic  acid  in  the  urine  was  correspondingly 
increased.  It  may  be  safely  inferred  that  glucuronic  acid  is 
produced  solely  in  the  intermediary  metabolism  of  protein. 
For  the  large  b'terature  on  this  subject,  and  also  on  the 
pentoses,  the  reader  is  referred  to  other  sources.1 

Pentoses,  which  are  sugars  containing  5  atoms  of  carbon, 
have  been  detected  in  animal  and  vegetable  tissue.  Hammar- 
sten  found  a  pentose  in  the  nucleoprotein  of  the  pancreas. 
Neuberg  showed  that  this  pentose  and  the  one  obtained  from 
nucleoprotein  in  the  liver  is  /-xylose.2  Grund3  has  found  pen- 
toses in  all  organs  of  the  body,  particularly  in  those  rich  in 
nuclear  material. 

Salkowski  and  Neuberg  have  shov/n  that  /-xylose  may  be 
derived  through  ferment  action  on  ^-glucuronic  acid.  Salkow- 
ski was  the  first  to  detect  a  pentose  in  the  urine,  and  this 
Neuberg  has  shown  to  be  i-arabinose.  The  elimination  of 
pentoses  in  the  urine  may  accompany  diabetes,  but  in  ex- 
tremely rare  cases  a  simple  pentosuria  occurs  in  which  pentose 
is  the  only  sugar  appearing  in  the  urine. 

Luzzatto4  reports  sucLa  case  in  which  the  elimination  of 
arabinose  was  independent  of  diet  or  mental  or  muscular 
effort.  Luzzatto  believes  the  pentose  in  this  case  to  have  been 
/-arabinose.  Neuberg  finds  that  in  the  normal  rabbit  /-ara- 
binose is  more  readily  burned  than  d-arabinose.  Luzzatto's 
case  could  be  explained  by  supposing  that  the  body  had  lost 
its  normal  power  to  burn  /-arabinose  as  normally  produced  in 
metabolism. 

Levene  and  La  Forge5  suggest  the  probable  presence  of 
d-ribose  in  the  urine  of  one  individual  with  pentosuria. 

Pentosuria  is  occasionally  discovered  in  the  routine  of  life 
insurance  examinations.  So  far  as  is  known  it  does  not  indi- 
cate danger  to  general  health. 

1  Neuberg:   "Ergebnisse  der  Physiologie,"  1904,  iii,  1  Abtheilung,  p.  373. 

2  See  also  Zerner  and  Waltuch:  "Biochemische  Zeitschrift,"  1013,  lviii,  410; 
Levene  and  La  Forge,  "Journal  af  Biological  Chemistry,"  1914,  xviii,  319. 

3  Grund:    "Zeitschrift  fur  physiologische  Chemie,"  1902,  xxxv,  in. 

4  Luzzatto:    "Hofmeister's  Beitrage,"  1905,  vi,  87. 

6  Levene  and  La  Forge:  "Journal  of  Biological  Chemistry,"  1913,  xv,  483. 


488  SCIENCE   OF   NUTRITION 

Cremer,1  in  a  series  of  excellent  experiments,  has  shown 
that  a  vegetable  pentose,  such  as  rhamnose,  may  be  burned  in 
a  rabbit  and  spare  an  isodynamic  equivalent  of  fat.  In  one 
rabbit,  on  a  fasting  day,  the  metabolism  amounted  to  129.1 
calories  (protein,  22.5,  and  fat,  106.6),  and  on  the  day  when 
rhamnose  was  given  to  128.4  calories  (protein,  21.36;  fat,  32.9, 
and  rhamnose,  74.11). 

Lindemann  and  May2  found  that  90  grams  of  rhamnose 
could  be  used  by  a  normal  man.  When,  however,  rhamnose 
was  given  to  a  diabetic  individual  whose  urine  had  been  sugar 
free,  sugar  appeared  in  the  urine.  In  cases  of  severe  diabetes 
reported  by  von  Jaksch3  it  was  found  that  rhamnose,  arabi- 
nose,  and  xylose  tended  to  increase  the  protein  metabolism, 
and  hence  the  sugar  output,  and  also  brought  about  diarrhea. 
The  use  of  pentoses  in  diabetes  has,  therefore,  not  been  success- 
ful. The  pentoses — rhamnose,  arabinose,  and  xylose — are  not 
convertible  into  glucose  in  the  organism.4 

Opie5  was  the  first  to  establish  a  connection  between 
changes  in  the  islands  of  Langerhans  of  the  pancreas  and  the 
cause  of  diabetes.  Janeway  and  Oertel,6  von  Noorden,  and 
others,  have  reported  autopsies  on  cases  of  severe  diabetes  in 
which  the  pancreas  appeared  perfectly  normal.  It  is  not 
always  possible  to  observe  with  the  microscope  the  cause  of 
pathologic  change  in  function. 

Allen7  found  degeneration  of  the  islands,  which  was 
accompanied  by  diabetes,  after  the  removal  of  nine-tenths  of 
the  pancreatic  tissue  in  the  dog,  and  Homans8  reports  that  the 
removal  of  three-fourths  of  the  pancreatic  tissue  in  the  cat 
produces  one  of  two  results,  either  a  disappearance  of  secretory 
granules  in  the  islands  of  Langerhans  with  suggestive  evidence 

1  Cremer:    "Zeitschrift  fur  Biologie,"  1901,  xlii,  428. 

2  Lindemann  and  May:   "Deutsches  Archiv  fur  klin.  Med.,"  1896,  lvi,  283. 

3  von  Jaksch:    Ibid.,  1899,  lxiii,  612. 
4Brasch:    "Zeitschrift  fur  Biologie,"  1908,  1,  113. 

5  Opie:    "Journal  of  Experimental  Medicine,"  1901,  v,  397. 

6  Janeway  and  Oertel:    "Virchow's  Archiv,"  1903,  clxxi,  547. 

7  Allen:   "Glycosuria  and  Diabetes,"  Boston,  1913. 

8  Homans:   "Journal  of  Medical  Research,"  1914,  xxx,  49. 


METABOLISM   IN  DIABETES   AND   PHOSPHORUS-POISONING    489 

of  overactivity  and  without  diabetes;  or,  occasionally,  a 
degeneration  of  the  islands  of  Langerhans  without  disturbance 
of  the  remaining  acinous  tissue,  but  accompanied  by  fatal 
diabetes. 

On  autopsy  in  diabetes  large  quantities  of  fat  are  frequently 
found  in  the  liver  and  muscles.  The  same  is  observed  in 
chloroform  narcosis  when  sugar  appears  in  the  urine,  in  anemia, 
and  after  respiration  of  rarefied  air,  where  lactic  acid  is  elimi- 
nated in  the  urine  (p.  423),  and  in  phosphorus-  and  arsenic- 
poisoning,  in  acute  yellow  atrophy,  in  pernicious  vomiting  of 
pregnancy,  in  eclampsia  and  in  cyclic  vomiting  in  children, 
which  are  similarly  accompanied  by  an  elimination  of  lactic 
acid.  These  phenomena  are  always  associated  with  an  in- 
creased protein  metabolism  and  an  increased  ammonia  and 
amino-acid  output  in  the  urine.1  Fat  likewise  appears  in  the 
mammary  glands  during  lactation  (see  p.  396). 

Virchow  assumed  a  fatty  degeneration  of  protein  in  which 
the  tissue  protein  was  converted  into  fat,  as  distinguished  from 
a  fatty  infiltration  in  which  body  fat  passed  into  the  cells. 
Much  of  the  earlier  writing  of  Voit  is  pervaded  with  the  theory 
of  a  considerable  origin  of  fat  from  protein  (p.  228).  The  idea 
of  a  fatty  degeneration  of  protein  in  the  old  sense  has  been 
largely  overturned  by  the  work  of  Rosenfeld.2  He  finds  that 
if  a  dog  be  starved  and  then  given  sheep's  fat,  and  again 
starved,  the  ingested  fat  will  be  found  deposited  as  sheep's  fat 
in  his  adipose  tissue,  while  the  liver  will  contain  about  10  per 
cent,  of  fat,  and  this  characteristic  dog  fat.  If  now  phospho- 
rus- or  phlorhizin-poisoning  be  induced  and  the  liver  be  ex- 
amined, 40  per  cent,  of  fat  may  be  found  therein,  and  this  in 
the  form  of  sheep's  fat.  Hence,  in  these  cases  the  fat  is  simply 
transported  to  the  liver  from  the  fat  deposits  of  the  body. 
The  fat  in  the  blood  is  largely  increased.  The  fat  becomes 
normal  in  quantity  in  the  liver  twenty-four  hours  after  the 


1  For  literature  consult  Ewing:     "Archives  of  Internal  Medicine,"  1908, 
ii,  476. 

2  Rosenfeld:   "Ergebnisse  der  Physiologie,"  1903,  ii,  I,  p.  50. 


49©  SCIENCE    OF   NUTRITION 

cessation  of  the  phlorhizin  action.  It  is  retransported  to  the 
places  of  fat  deposit. 

B.  Fischer1  reports  a  case  of  coma  diabeticum  in  which  the 
blood-serum  contained  23  per  cent,  of  fat.  Klemperer  and 
Umber2  state  that  of  9  diabetics  with  acidosis  7  had  lipemia. 
Adler3  and  Imbrie4  report  cases  in  which  the  blood-serum  con- 
tained respectively  29  and  14  per  cent,  of  fat  plus  cholesterol; 
of  the  latter  there  were  3.1  and  1.5  per  cent,  in  the  serum  in  the 
2  cases.  Lecithin  was  absent,  and  Imbrie  found  that  the  fatty 
acids  entering  into  the  composition  of  the  blood  fat  had  an 
iodin  number  similar  to  that  of  the  fatty  acids  entering  into 
the  composition  of  subcutaneous  fat.  Hence,  the  lipemia  was 
due  to  the  mobilization  of  tissue  fat. 

A  supposed  production  of  fat  from  protein  has  long  been 
believed  to  occur  in  the  ripening  of  cheese.  However,  Kondo5 
finds  that  in  the  process  of  ripening  cheddar  cheese  9  per  cent, 
of  the  fat  content  disappears  after  thirty  days  and  1 2  per  cent, 
after  forty  days. 

If  a  fatty  "degeneration"  were  to  be  found  anywhere,  it 
would  certainly  be  looked  for  in  the  dying  cells  of  the  liver  in 
phosphorus-poisoning,  or  in  the  analogous  condition  of  acute 
yellow  atrophy  of  the  liver.  But  another  explanation  avails. 
Mandel  and  Lusk6  have  shown  that  lactic  acid  disappears 
from  the  blood  and  urine  of  a  phosphorized  dog  if  phlorhizin 
glycosuria  be  induced.  The  writer  believes  that  the  lactic  acid 
which  occurs  is  derived  from  the  sugar  formed  in  protein 
metabolism.  In  the  above  case  the  sugar  is  removed  without 
conversion  into  lactic  acid.  In  phlorhizin  diabetes,  glucose 
does  not  burn;  in  phosphorus-poisoning  lactic  acid  derived 
from  glucose  does  not  burn.  In  both  cases  a  sugar-hungry 
cell,  or  one  where  carbohydrate  is  not  oxidized,  is  found,  and 
under  these  circumstances  fat  is  attracted  to  the  cell,  and  in 

1  Fischer,  B.:    "Virchow's  Archiv,"  1903,  clxxii,  30  and  218. 

2  Klemperer  and  Umber:  "Zeitschrift  fur  klinische  Medicin,"  1908,  lxv,  340. 

3  Adler:    "Berliner  klin.  Wochenschrift,"  1900,  xlvi,  1453. 

4  Imbrie:    "Journal  of  Biological  Chemistry,"  1915,  xx,  87. 

5  Kondo:    "Biochemische  Zeitschrift,"  1913-14,  lix,  113. 

6 Mandel  and  Lusk:    "American  Journal  of  Physiology,"  1906,  xvi,  129. 


METABOLISM   IN   DIABETES   AND    PHOSPHORUS-POISONING     49 1 

larger  quantities  than  can  be  useful.  Wherever  sugar  freely 
burns,  this  fatty  infiltration  is  impossible  (p.  249).  A  reduced 
local  circulation  in  a  portion  of  the  heart  may  produce  anemia 
of  the  part,  an  imperfect  local  oxidation  of  lactic  acid  normally 
formed,  and  a  fatty  infiltration  of  the  locality.  The  writer 
offers  this  hypothesis  as  his  explanation  of  fatty  changes  in 
tissue  in  general. 

A  corroborating  fact  found  by  Shibata1  is  that,  although 
the  amount  of  fat  in  the  liver  is  increased  in  phosphorus-poison- 
ing, the  quantity  of  total  fat  in  the  organism  is  much  reduced 
during  the  progress  of  this  disease.  In  cases  of  fatty  infiltra- 
tion (so-called  degeneration)  Czyhlarz  and  Fuchs2  could  find 
no  evidence  of  an  abnormally  changed  relationship  between 
the  quantities  of  cholesterol  and  fat  present  in  the  diseased 
tissue. 

Medical  literature  was  formerly  greatly  influenced  by  the 
idea  of  a  reduced  general  oxidation  in  the  body.  Except  in 
the  case  of  myxedema  which  is  accompanied  by  a  fall  in  body 
temperature,  and  in  some  cases  of  obesity,  no  such  condition 
occurs.  The  writer3  has  shown  that  in  phosphorus-poisoning, 
the  classical  example  of  supposed  reduced  oxidation,  there  was 
actually  no  reduction  in  the  total  heat  production,  but  rather 
an  increase.  From  the  fourth  day  to  the  sixth  of  simple  fast- 
ing in  one  dog  the  total  metabolism  for  twenty-four  hours 
averaged  45.2  calories  per  kilogram,  and  on  the  ninth  day  to 
the  eleventh  of  fasting  which  preceded  death  from  phosphorus- 
poisoning  the  heat  production  was  48.8  calories.  These  results 
have  been  confirmed  by  Hirz.4 

It  is  therefore  evident  that  the  presence  of  lactic  acid  is 
only  a  symptom  in  the  group  of  diseases  just  mentioned  (p. 
489),  and  is  no  more  an  indication  of  a  reduction  in  oxidative 
power  as  represented  by  the  total  heat  production  than  is  the 
elimination  of  sugar  in  diabetes.     The  abundant  ammonia  in 

Shibata:    "Biochernische  Zeitschrift,"  1911,  xxxvii,  345. 
2  Czyhlarz  and  Fuchs:   Ibid.,  1914,  lxii,  131. 
3Lusk:    "American  Journal  of  Physiology,"  1907,  xix,  461. 
4  Hirz:    "Zeitschrift  fur  Biologie,"  1913,  lx,  187. 


492  SCIENCE   OF   NUTRITION 

the  urine  is  used  to  neutralize  the  acid  produced.  The  reduc- 
tion in  the  amount  of  lactic  acid  oxidized  raises  the  total  pro- 
tein metabolism.  The  deficient  deamination  which  results  in 
the  elimination  of  amino-acids  in  the  urine  may  possibly  be 
due  to  the  injury  of  deaminating  enzymes  by  the  presence  of 
lactic  acid. 

It  has  been  stated  that  the  action  of  phosphorus  is  to  induce 
autolysis  (self-digestion)  of  the  body's  protoplasm  (Jacoby,1 
Waldvogel2),  since  leucin,  tyrosin,  glycocoll,3  phenyl-dlanin  and 
arginin,4  and  other  amino-acids  may  be  eliminated  in  consider- 
able quantity  in  the  urine.  Wakeman5  finds  a  change  in  the 
relative  amounts  of  histidin,  arginin,  and  lysin  contained  in  the 
liver  substance  after  phosphorus-poisoning,  arginin  in  particu- 
lar being  reduced  below  the  quantity  found  in  the  liver  of  the 
normal  dog.  Oswald6  thinks  that  phosphorus  destroys  or 
weakens  the  anti-autolytic  agents  of  the  body.  That  autolytic 
enzymes  do  not  gain  free  control  over  the  cells  through  the  di- 
rect influence  of  phosphorus  is  proved  by  the  work  of  Ray, 
McDermott,  and  Lusk.7  These  authors  found  that  phosphorus 
injections  raised  the  protein  metabolism  of  fasting  dogs  to  250, 
260,  283,  248,  183,  and  164  per  cent,  of  that  of  the  dog  when 
normal.  They  contrasted  this  increased  protein  metabolism 
with  that  obtained  in  phlorhizin  glycosuria,  which  is  repre- 
sented by  increases  to  540,  450,  340,  and  340  per  cent.  When, 
however,  they  gave  phlorhizin  and  obtained  the  increased 
metabolism,  and  then  injected  phosphorus,  this  was  not  followed 
by  any  marked  increase  in  protein  metabolism.  Under  these  cir- 
cumstances phlorhizin  glycosuria  is  the  predominating  factor, 
removing  the  glucose  produced  from  protein  before  it  could  be 
converted  into  lactic  acid. 

1  Jacoby:    "Zeitschrift  fur  Physiologische  Chemie,"  1900,  xxx,  174.  __ 

2  Waldvogel:  "Deutsches  Archiv  fur  klinische  Medizin,"  1905,  lxxxii,  437. 

3  Abderhalden  and  Bergell:  "Zeitschrift  fur  physiologische  Chemie,"  1903, 
xxxix,  464. 

4Wolgemuth:    Ibid.,  1905,  xliv,  74. 

5  Wakeman:  Ibid.,  1905,  xliv,  335. 

6  Oswald:    "Biochemisches  Centralblatt,"  1905,  iii,  365. 

7  Ray,  McDermott,  and  Lusk:  "American  Journal  of  Physiology,"  1899, 
iii,  139. 


METABOLISM    IN    DIABETES    AND    PHOSPHORUS-POISONING     493 

Analogous  to  this  is  the  observation  of  Sass,1  who  found 
that  under  normal  conditions  strychnin  convulsions  reduced 
the  titratible  alkalinity  of  the  blood  on  account  of  the  forma- 
tion of  lactic  acid,  but  in  depancreatinized  dogs  this  result 
could  not  be  achieved  because  lactic  acid  could  not  be  pro- 
duced from  glucose. 

As  regards  phosphorus-poisoning  Araki2  believes  that  lactic 
acid  accumulation  is  due  to  lack  of  oxygenation  of  the  tissues 
caused  by  a  slow  heart-beat,  but  not  due  to  anemia.  He  does 
not  believe  the  oxygen  deprivation  to  be  very  pronounced. 
The  writer  otters  the  explanation  that  phosphorus  may  affect 
the  conditions  which  lead  to  the  oxidation  of  the  lactic  acid 
derived  from  glucose  (see  p.  263),  and  the  accumulation  of 
this  acid  may  prevent  the  action  of  some  of  the  deaminating 
enzymes;  and,  further,  its  non-combustion  may  necessitate  an 
increase  of  protein  metabolism. 

This  theory  is  strengthened  by  the  discovery  of  Schryver3 
that  the  addition  of  lactic  acid  favors  the  accumulation  of 
amino-acids  in  autolysis  of  the  liver. 

Claude  Bernard  showed  that  glucose,  whether  derived  from 
protein  or  starch,  was  convertible  into  glycogen,  and  this  again 
was  changeable  into  glucose.  Present  knowledge  adds  lactic 
acid  to  both  ends  of  this  chain  in  showing  the  following  pos- 
sible progression — lactic  acid,  glucose,  glycogen,  glucose,  lactic 
acid  (see  p.  263). 

Quite  pertinent  to  this  theoretic  discussion  is  the  obser- 
vation of  von  Jaksch4  on  a  patient  who  recovered  from  phos- 
phorus-poisoning, and  in  whom  a  desire  for  carbohydrates 
marked  the  beginning  of  convalescence. 

It  should  also  be  noted  that  more  carbohydrates  must  be 
ingested  in  cases  of  hepatic  disease  to  maintain  nitrogen  equi- 
librium than  are  required  in  health.5 

1  Sass:   "Zeitschrift  ftir  ex.  Path,  und  Ther.,"  1914,  xv,  370. 

2  Araki:    "Zeitschrift  fur  physiologische  Chemie,"  1893,  xvii,  337. 

3  Schryver:   "The  Bio-Chemical  Journal,"  1906,  i,  153. 

4  von  Jaksch:    "Zeitschrift  ftir  physiologische  Chemie,"  1903,  xl,  123. 
6Tallqvist:   "Archiv  fur  Hygiene,"  1908,  lxv,  39. 


494  SCIENCE   OF   NUTRITION 

A  curious  anomaly  of  carbohydrate  metabolism  has  been 
discovered  by  Underhill1  following  the  administration  of  hy- 
drazin,  which  he  defines  as  a  poison  with  an  almost  specific 
effect  upon  the  cytoplasm  of  the  parenchymatous  cells  of  the 
liver.  It  attacks  first  the  cells  in  the  center  of  the  lobules, 
while  phosphorus  shows  its  first  effects  upon  the  cells  of  the 
periphery.  If  50  milligrams  of  hydrazin  per  kilogram  of 
animal  be  given  to  dogs,  the  quantity  of  glucose  in  the  blood 
and  of  glycogen  in  the  liver  is  greatly  reduced  and  the  admin- 
istration of  glucose  may  cause  the  death  of  the  animal  within 
twelve  hours.  Otherwise  the  dog  recovers  in  five  days. 
Underhill  and  Murlin2  found  that  the  administratipn  of  hy- 
drazin to  fasting  dogs  increased  the  respiratory  quotient. 
An  increased  oxidation  of  carbohydrate,  therefore,  probably 
explains  the  diminished  blood-sugar  content  and  the  disap- 
pearance of  glycogen  from  both  liver  and  muscles.  Hydrazin 
was  without  influence  upon  the  level  of  the  basal  metabolism. 

1  Underhill:   "Journal  of  Biological  Chemistry,"  1911-12,  x,  159. 

2  Underhill  and  Murlin:  Ibid.,  1915,  xxii,  499. 


CHAPTER  XVII 

METABOLISM  IN  NEPHRITIS,  IN  CARDIAC  DISEASE, 
AND  IN  OTHER  CASES   INVOLVING  ACIDOSIS 

In  i 82 i  Prevost  and  Dumas1  observed  that  if  the  kidneys 
of  a  dog  be  extirpated,  urea  accumulates  in  the  blood.  This 
observation  led  to  the  discovery  by  Bright  in  1836  that  the 
amount  of  urea  in  the  blood  of  nephritic  patients  was  abnor- 
mally high. 

Using  more  accurate  methods,  Folin2  finds  that  when  a  low 
protein  dietary  is  taken  the  normal  figures  for  total  non-pro- 
tein nitrogen  in  the  blood  of  a  man  are  22  to  28  milligrams  per 
100  c.c.  of  blood,  of  which  11  to  14  milligrams  are  in  the  form 
of  urea.  The  maximum  amount  of  non-protein  nitrogen  in 
a  normal  person  is  not  usually  above  40  milligrams  per  100  c.c.3 
Sometimes  after  protein  ingestion  in  nephritis  the  non-protein 
nitrogen  does  not  increase  in  the  blood ;  in  other  cases  there  is 
a  considerable  rise.  The  increased  level  of  urea  in  the  blood 
is  a  compensatory  reaction  to  a  diminished  power  of  excretion 
by  the  kidney.4 

Emphasis  has  been  laid  upon  a  negative  nitrogen  balance  as 
indicating  a  retention  of  urea  by  the  nephritic  patient,  but 
such  a  retention  is  susceptible  of  two  interpretations.  Thus, 
Mosenthal  and  Richards5  have  given  patients  with  moderately 
severe  chronic  interstitial  nephritis  diets  containing  between 
16  and  47  grams  of  nitrogen  and  have  observed  nitrogen  reten- 

1  Prevost  and  Dumas:  "Ann.  de  chemie  et  de  phys.,"  1821,  xxiii,  90. 

2  Folin,  Denis,  and  Seymour:  "Archives  of  Internal  Medicine,"  1914,  xiii, 
224. 

3  For  the  complete  chemical  and  physical  analysis  of  blood  in  30  normal 
cases  consult  the  important  work  of  Gettler  and  Baker:  "Journal  of  Biological 
Chemistry,"  1016,  xxv,  211. 

4  McLean:    "Journal  of  Experimental  Medicine,"  1915,  xxii,  366. 

5  Mosenthal  and  Richards:  "Archives  of  Internal  Medicine,"  1916,  xvii,  329. 

495 


496  SCIENCE    OF    NUTRITION 

tion.  Had  this  retention  been  in  the  form  of  non-protein 
nitrogen,  the  blood  would  have  contained  between  78  and  148 
milligrams  of  such  nitrogen,  but  the  actual  values  never  rose 
above  $&  milligrams.  Davis  and  Foster,1  however,  find  that 
nitrogen  retention  under  these  circumstances  may  take  place  in 
the  liver  and  muscle  in  the  form  of  non-protein  nitrogen.  The 
very  ill  patients  were  benefited  by  large  water  ingestion. 

Henderson  and  Palmer2  describe  cases  of  nephritis  in  which 
the  volume  of  the  urine  is  large,  the  titratable  acidity  high, 
but  in  which  the  total  acid  elimination  is  decreased  because  of 
a  greatly  reduced  elimination  of  ammonia.  They  conclude 
that  this  points  to  a  condition  of  acidosis  of  renal  origin.  As 
a  matter  of  fact,  Peabody3  has  discovered  that  the  acidosis  of 
nephritis  is  due  to  a  retention  of  non- volatile  acids  which  would 
ordinarily  be  removed  by  the  kidney. 

Peabody,  Aub,  and  DuBois,  in  experiments  yet  to  be  pub- 
lished, have  made  investigations  concerning  the  metabolism 
of  10  patients  suffering  from  severe  nephritis  which  show  that 
most  of  the  individuals  had  normal  basal  metabolisms.  In 
the  presence  of  greatly  decreased  alkalinity  and  of  a  high 
content  of  non-protein  nitrogen  in  the  blood  the  total  heat 
production  showed  no  variation  from  the  normal. 

Tachau4  finds  that  in  nephritis  the  loss  of  nitrogen  by  way 
of  the  sweat  induced  by  an  electric  light  bath  is  not  material, 
but  that  the  loss  of  sodium  chlorid  may  reach  2  grams  per  hour 
and  may  reduce  an  edema. 


In  patients  who  manifest  marked  evidence  of  circulatory 
disturbances  Foster5  shows  that  there  is  an  increase  in  the  quan- 

1  Davis  and  Foster:  "Proceedings  of  Soc.  for  ex.  Biol,  and  Med.,"  1015,  xiii, 

33'  ... 

2  Henderson,  L.  J.,  and  Palmer:    "Journal  of  Biological  Chemistry,"  1915, 

xxi,  37. 

3  Peabody:  "Archives  of  Internal  Medicine,"  1014,  xiv,  236;  Ibid.,  1915,  xvi, 

955- 

4  Tachau:    "Deutsches  Archiv  fur  klinische  Medizin,"  1912,  cvn,  305. 

5  Foster,  N.  B.:    "Archives  of  Internal  Medicine,"  1915,  xv,  356. 


METABOLISM   IN   NEPHRITIS   AND   IN   CARDIAC   DISEASE      497 

tity  of  non-protein  nitrogen  of  the  blood,  even  in  the  absence 
of  nephritis. 

Peabody,  Meyer,  and  DuBois1  studied  16  patients  with 
cardiac  and  cardiorenal  disease  by  the  methods  of  direct  and 
indirect  calorimetry.  The  two  methods  agreed  within  1.9 
per  cent.  There  was  no  abnormal  deviation  of  the  respiratory 
quotients  as  had  been  announced  by  several  previous  investi- 
gators. Patients  with  compensated  cardiac  lesions  or  with 
mild  nephritis  showed  a  normal  metabolism.  Of  12  patients 
with  dyspnea,  9  showed  a  distinct  rise  in  metabolism,  and  in  5 
of  these  the  increase  was  between  25  and  50  per  cent,  above 
the  normal.  Two  of  these  5  patients  manifested  marked 
acidosis,  as  was  indicated  by  a  low  carbon  dioxid  tension  in 
the  alveolar  air.  In  2  other  patients,  whose  metabolisms 
were  equally  high,  there  was  no  significant  depression  of  the 
alveolar  carbon  dioxid. 

If  the  dyspnea  were  accompanied  by  the  production  of 
lactic  acid  in  any  of  the  organs,  this  might  have  been  the 
stimulus  to  the  higher  metabolism  observed.  The  decompen- 
sated heart  produces  slow  or  insufficient  circulation  with  im- 
perfect oxidation  in  the  tissues,  which  conditions  readily  lend 
themselves  to  lactic  acid  formation. 

Howland  and  Marriott2  describe  a  type  of  acidosis  which 
occurs  in  infants  during  the  course  of  attacks  of  severe  diar- 
rhea not  of  ileocolitic  type.  The  usual  type  of  abdominal 
breathing  of  the  young  child  is  succeeded  by  one  which  is  both 
costal  and  abdominal.  There  is  a  greater  amplitude  in  the 
respirations  and  they  are  made  with  a  distinct  effort.  There 
is  no  cyanosis.  The  condition  was  first  described  by  Czerny3 
who  called  attention  to  the  symptoms  as  resembling  those  ob- 
served in  rabbits  dying  after  the  administration  of  mineral 
acids.     Howland  and  Marriott  find  that  a  condition  of  acidosis 

Peabody,  Meyer,  A.  L.,  and  DuBois:  "Archives  of  Internal  Medicine," 
1016,  xvii,  980. 

2  Howland  and  Marriott:  "American  Journal  of  Diseases  of  Children,"  1916, 
xi,  309. 

3  Czerny:    "Jahrbuch  fur  Kinderheilkunde,"  1897,  xlv,  271. 

32 


493 


SCIENCE    OF   NUTRITION 


is  actually  present  in  these  children  and  they  were  the  first 
to  use  alkaline  treatment  in  order  to  rescue  them.  The  acido- 
sis is  not  due  to  acetone  bodies,  from  which  the  blood  is  free. 
The  following  presents  the  results  of  treatment  in  one  of 
their  cases: 


Date. 

Alveolar 
C02  Tension. 

HYPERl'NEA. 

Alkali. 

f 

Case  I -| 

I 

22 
23 
24 
24 

25 

Mm. 
21 

42 
54 
55 
4i 

+++ 

0 
0 
0 
0 

Given. 
Given. 
Stopped. 

In  normal  infants  the  carbon  dioxid  tension  is  between  36 
and  45  mm.  and  the  PH  of  the  blood  is  7.4.  In  the  children 
with  acidosis  the  PH  of  the  blood  was  7.2.  There  was  also  a 
reduction  of  the  reserve  alkali  of  the  blood.  There  was  fre- 
quent anuria  and  the  conclusion  is  drawn  that  the  cause  of 
the  acidosis  is  probably  a  retention  of  acid  phosphate  in  the 
organism. 


CHAPTER  XVIII 

METABOLISM   IN  FEVER 

By  fever  is  generally  understood  a  complex  of  phenomena 
the  dominant  characteristic  of  which  is  a  rise  of  body  tem- 
perature. If  the  term  "fever"  be  confined  simply  to  the  latter 
aspect,  one  might  classify  fevers  as  follows: 

(i)  Physiologic  fever,  induced,  for  example,  by  immersion 
in  a  hot  bath  at  a  temperature  of  400,  which  prevents  the 
normal  loss  of  body  heat  through  radiation  and  conduction. 
(2)  Neurogenic  fever,  as  brought  about  by  the  direct  stimulation 
of  nerve-cells  in  the  corpora  striata  of  the  mid-brain.  (3)  Non- 
infective  surgical  fever,  commonly  called  aseptic  fever,  due  to 
the  resolution  of  blood-cells  or  crushed  tissue  in  the  organism. 
(4)  Infective  fever,  produced  after  the  infection  of  the  organism 
by  certain  bacteria  or  their  products  and  by  some  protozoa. 
Or  one  may  consider  fever  as  being  due  to  infection  by  bac- 
teria or  protozoa,  and  include  all  other  increases  of  tempera- 
ture under  the  term  of  hyperthermia. 

In  a  previous  chapter  the  mechanism  of  normal  heat  regu- 
lation has  been  explained.  It  was  there  noted  that  on  a  warm, 
moist  day  the  temperature  of  a  fat  individual,  when  he  was 
working  hard,  rose  considerably  above  the  normal.  This  effect, 
if  carried  to  an  extreme,  results  in  sunstroke,  in  which  the  over- 
heating of  the  body  causes  a  rapid  pulse,  accompanied  by  dizzi- 
ness, delirium,  or  unconsciousness.  But  in  the  great  majority 
of  cases  the  body  temperature  remains  delicately  balanced, 
notwithstanding  changes  in  outside  environment,  or  internal 
heat  production.  In  the  fat  person  at  hard  work  the  condition 
of  increased  metabolism  is  combined  with  that  of  difficult  dis- 
charge of  heat.    A  person  placed  in  a  bath  at  400  would  be  sub- 

499 


500  SCIENCE   OF   NUTRITION 

ject  to  conditions  where  there  could  be  no  heat  loss,  but  rather 
a  gain  in  heat,  even  though  his  metabolism  were  low.  In  a 
normal  person,  therefore,  a  rise  in  temperature  may  be  due  to 
increased  heat  production,  with  difficulty  in  discharging  it,  or 
a  check  of  heat  loss  may  be  the  only  factor  of  the  higher  tem- 
perature. In  the  discussion  of  fever  one  must  consider  two 
possible  causes:  (i)  an  increase  in  heat  production,  and  (2) 
a  decrease  in  the  facilities  for  the  discharge  of  heat  produced. 

It  has  already  been  set  forth  that  the  metabolism  in  a  cold- 
blooded animal  increases  with  the  temperature  of  his  environ- 
ment. Warmed  tissue  metabolizes  more  material  than  cooled 
tissue.  It  is  therefore  to  be  expected  that  the  metabolism  in  an 
organism  which  has  been  warmed  to  fever  heat  will  be  greater 
than  the  normal.  This  was  beautifully  shown  in  the  experi- 
ments of  Pfliiger,1  who  subjected  both  curarized  and  normal 
rabbits  to  external  warmth  which  raised  their  temperatures. 
In  the  animals  whose  voluntary  muscles  were  paralyzed  by 
curare  as  the  rectal  temperature  rose  from  390  to  410  the  oxy- 
gen absorption  increased  10  per  cent,  for  each  degree  of  tem- 
perature increase.  In  the  normal  animals  the  increased  me- 
tabolism between  temperatures  of  38. 6°  and  40.60  was  shown 
by  increases  of  5.7  per  cent,  for  oxygen  and  6.8  per  cent,  for 
carbon  dioxid  for  a  rise  of  i°  of  temperature. 

It  has  been  noted  in  another  chapter  (p.  144)  that  Rubner 
found  in  man  that  a  bath  at  a  temperature  of  350  had  no  effect 
on  metabolism,  while  one  at  440  increased  the  volume  of  respi- 
ration 18.8  per  cent.,  the  oxygen  absorption  17.3  per  cent.,  and 
the  carbon  dioxid  elimination  32.1  per  cent.  Linser  and 
Schmid2  confirm  these  results  in  experiments  on  two  men  suf- 
fering from  ichthyosis  hystrix,  which  involved  almost  complete 
loss  of  function  of  the  sweat-glands.  The  body  temperature 
of  these  men  could  be  varied  by  altering  the  temperature  of 
their  living-room  between  300  and  380.     The  humidity  of  the 

1  Pfliiger:   "Pfluger's  Archiv,"  1878,  xviii,  303,  356. 

2  Linser  and  Schmid:  "Deutsches  Archiv  fur  klinische  Medizin,"  1904, 
lxxix,  514. 


METABOLISM   IN   FEVER  501 

room  was  from  40  to  50  per  cent.  The  maximum  increase  in 
the  metabolism  of  these  individuals  is  represented  by  a  rise  in 
carbon  dioxid  excretion  from  3.8  c.c.  per  minute  and  kilogram 
at  the  body  temperature  of  36. 2°  to  5.3  c.c.  per  minute  and 
kilogram  at  390.  The  number  of  respirations,  which  were  from 
12  to  15  per  minute  at  360,  increased  to  20  and  22  at  390.  The 
total  increase  in  the  carbon  dioxid  output,  due  to  a  rise  of  30 
through  simple  warming  of  cells,  amounted  to  40  per  cent. 

The  next  question  is  of  the  nature  of  the  materials  which  are 
oxidized.  It  has  long  been  known  that  urea  excretion  is  ab- 
normally high  in  fever,1  and  this  led  to  the  inquiry  whether  the 
rise  was  merely  the  result  of  increased  body  temperature  or  was 
due  to  toxic  influences. 

F.  Voit2  found  that  on  artificially  raising  the  temperature  of 
a  fasting  dog  to  400  or  410  for  a  period  of  twelve  hours  there 
was  an  increase  in  nitrogen  elimination  of  37  per  cent,  above 
the  normal.  Warming  for  a  period  of  only  three  hours  had 
slight  effect.  If,  however,  the  animal  were  fed  with  meat  and 
fat,  warming  increased  the  protein  metabolism  only  4  per  cent. 
If  the  animal  were  given  30  to  40  grams  of  cane-sugar  no 
increased  metabolism  of  protein  followed  the  rise  in  temper- 
ature to  410.  It  is  apparent  that  the  ingestion  of  protein  and 
carbohydrates  may  control  this  rise  in  protein  destruction  due 
to  a  febrile  temperature.  F.  Voit  explains  the  increase  in  pro- 
tein metabolism  in  hyperthermia  as  due  to  the  quick  combus- 
tion of  glycogen  and  the  consequent  impoverishment  of  the 
tissues  as  regards  carbohydrate  material.  Protein  or  carbohy- 
drate ingesta  furnish  the  necessary  carbohydrate  and  prevent 
the  hyperthermal  rise  in, protein  metabolism. 

Careful  experiments  by  Graham  and  Poulton,3  conducted 
in  Friedrich  Miiller's  clinic  in  Munich,  have  shown  that  in 
man  a  body  temperature  of  40. 20,  brought  about  by  the  influ- 
ence of  a  steam  bath,  does  not  of  itself  cause  an  increase  in  the 

1  Traube  and  Jochmann:  "Deutsche  Klinik,"  1855,  vii,  511. 

2  Voit,  F.:  "Sitzungsberichte  der  Gesellschaft  fur  Morphologie  und  Phys- 
iologic," 1895,  Heft  ii,  p.  120. 

3  Graham  and  Poulton:    "Quarterly  Journal  of  Medicine,"  191 2,  vi,  82. 


502  SCIENCE   OF   NUTRITION 

metabolism  of  body  protein.  Three  different  diets  were 
taken.  In  experiments  I  and  II  the  caloric  value  of  the  diet 
was  high,  with  excess  of  carbohydrate  and  only  a  minimal  quan- 
tity of  protein.  Diets  III  and  IV  were  composed  chiefly  of 
protein  and  fat;  one  with  ample  calories  and  high  in 
protein,  the  other  with  insufficient  calories  and  only  a 
moderate  amount  of  protein.  The  results  of  the  experi- 
ments may  be  thus  epitomized: 

Subject P.  G.  P.  G. 

Experiment I  II  HI  IV 

Character  of  diet CH+fat.  CH+fat.  Prot.+fat.  Prot.+fat. 

Calories  in  diet 495Q  4690  3700  1970 

Calories  per  kg.  per  day.  68  75  50  32 

N  in  diet,  grams 1.23  0.91  34.4  12.3 

No.  of  days  of  diet  before 

experiment 6  6  19  8 

=±=   Body  N,  day  before 

bath -3-37  -3-00  +1.91  -3-41 

±  Body  N,  day  of  hot 
bath —2.88  —2.78  +1.42  —2.45 

±  Body  N,  day  after 
bath —2.85  —2.47  +1.66  —3.22 

Maximal  body  tempera- 
ture, day  of  bath 39-3°  40.20  40.10  39-7° 

In  these  experiments  the  abnormally  high  body  tempera- 
ture was  maintained  for  several  hours,  and  yet  there  was  never 
any  increase  in  the  breakdown  of  body  protein  due  to  the 
hyperthermia. 

It  has  already  been  recited  (see  p.  317)  how  Kocher,  work- 
ing in  the  same  clinic,  found  that  a  walk  of  60  kilometers  with 
a  consequent  doubling  of  the  heat  production  was  without 
effect  upon  the  protein  metabolism  even  when  the  output  of 
urinary  nitrogen  was  at  a  minimal  level. 

It  is  evident  from  these  experiments  that  neither  high  body 
temperature  nor  largely  increased  heat  production  has  any 
effect  upon  the  minimal  "wear  and  tear"  quota  of  protein 
metabolism.  The  destruction  of  protein  by  toxic  processes 
in  fever  is,  therefore,  independent  of  the  two  factors  enumer- 
ated, as  will  be  seen  later. 

If  certain  portions  of  the  brain  be  punctured,  and  particu- 


METABOLISM   IN   FEVER  503 

larly  the  region  of  the  corpora  striata,  a  high  fever  sets  in. 
Here  again  there  is  an  increased  output  of  carbon  dioxid  and  a 
rise  in  protein  metabolism.  This  phenomenon  has  been  re- 
cently investigated  by  Hirsch,  Miiller,  and  Roily,1  and  by 
Roily2  alone.  They  find  that  after  the  "heat  puncture"  of  the 
corpora  striata  the  liver,  blood,  and  skin  become  warmer  than 
the  muscles,  although  normally  the  muscles  are  warmer  than 
the  skin.  They  find  that  the  heat  puncture  is  effective  even  in 
curarized  animals,  where  the  muscles  are  free  from  nerve  stim- 
uli. Roily  finds,  however,  that  the  heat  puncture  is  ineffective 
if  the  liver  of  the  rabbit  has  been  previously  freed  from  glyco- 
gen by  strychnin  convulsions.  Under  these  circumstances 
there  is  no  rise  in  temperature  nor  concomitant  rise  in  protein 
metabolism.  The  inference  is  that  the  fever  in  question  is  due 
to  nerve  impulses  which  increase  the  metabolism  of  carbo- 
hydrate in  the  liver.  In  infectious  fever  there  is  little  glyco- 
gen in  the  organism,  but  that  the  fever  in  this  case  is  due  to 
other  causes  than  the  rapid  combustion  of  carbohydrates  was 
shown  by  Roily,  who  infected  a  rabbit,  which  had  been  freed 
from  glycogen  as  above  described,  with  a  culture  of  pneumo- 
cocci  and  obtained  as  great  a  rise  in  temperature  and  protein 
metabolism  as  would  have  occurred  had  the  tissues  of  the 
rabbit  been  rich  in  carbohydrates.  The  rise  in  temperature 
after  puncture  of  the  corpora  striata  may  be  termed  neurogenic 
fever,  and  it  is  like  the  glycosuria  following  Claude  Bernard's 
puncture,  in  that  its  mechanism  is  no  more  invoked  in  true 
infectious  fever  than  are  the  nerve  centers  in  diabetes  mellitus 
(p.  446). 

Freund3  finds  that  simple  heat  puncture  in  the  rabbit  is 
still  effective  after  cutting  the  cord  at  the  level  of  the  second 
dorsal  nerve.  It  is  interesting  that  this  phenomenon  of  heat 
puncture,  with  its  increased  carbohydrate  combustion  and  an 
elevation  of  body  temperature  between  0.70  and   1.760  in 

1  Hirsch,  Miiller,  and  Roily:  "Deutsches  Archiv  fiir  klin.  Med.,"  1903,  lxxv, 
264. 

2  Roily:    Ibid.,  1903,  lxxviii,  250. 

3  Freund,  H.:   "Archiv  fiir  exp.  Path,  und  Pharm.,"  1913,  lxxii,  304. 


504  SCIENCE   OF   NUTRITION 

rabbits  and  in  dogs,  is  without  influence  upon  the  hydrogen 
ion  concentration  of  the  blood.1 

If  the  extent  of  metabolism  in  infectious  fevers  be  inves- 
tigated the  following  state  of  affairs  is  discovered.  The  course 
taken  by  the  metabolism  in  toxic  fevers  is,  as  a  rule,  (i)  a  slight 
rise  in  protein  metabolism,  even  before  the  fever  sets  in;  (2) 
increased  metabolism  with  heat  retention  and  increased  pro- 
tein destruction;  (3)  heat  production  and  heat  elimination 
become  equal,  with  the  body  at  a  higher  temperature  level. 
These  factors  were  illustrated  in  the  experiments  of  May2  on 
fasting  rabbits  injected  with  a  culture  of  erysipelas  of  the  pig 
and  in  the  following  experiments  of  Staehelin. 

Staehelin3  infected  a  dog  by  inoculating  him  with  1.5  c.c.  of 
dog's  blood  containing  surra  trypanosomes  which  are  active 
flagellate  parasites.  Fever  set  in  on  the  sixth  day  after  the 
inoculation  and  the  dog  died  on  the  twenty-fifth  day.  The 
metabolism  due  to  the  infection  rose  to  88.9  calories  per  kilo- 
gram on  the  tenth  day  after  inoculation  as  against  a  normal  of 
59.8,  an  increase  of  48  per  cent.  On  this  febrile  day  26  per 
cent,  of  the  total  energy  was  yielded  by  protein ;  the  body  lost 
2.8  grams  of  nitrogen,  which  indicated  a  high  toxic  waste. 
However,  all  the  increase  in  the  heat  production  did  not  come 
from  increased  protein  metabolism,  but  the  fat  destruction 
was  also  increased,  and  Staehelin  speaks  of  a  toxic  waste  of  fat. 
He  also  remarks  that  the  dog  remained  perfectly  quiet  during 
the  period  of  the  experiment,  but  he  does  not  say  whether 
thermal  influences  which  could  result  in  chill  were  completely 
excluded.  However,  he  came  to  the  conclusion  that  in  this 
fever  caused  by  trypanosomes  the  metabolism  was  higher 
than  could  be  explained  by  the  overwarming  of  the  body. 

During  the  last  days  of  life  the  body  temperature  fell  and 
with  it  the  amount  of  the  metabolism.  The  following  table 
gives  a  partial  record  of  the  daily  metabolism  in  this  dog: 

1  Quagliariello :    "Biochemische  Zeitschrift,"  1912,  xliv,  162. 

2  May:    "Zeitscheift  fur  Biologie,"  1894,  xxx,  1. 

3  Staehelin:    "Archiv  fiir  Hygiene,"  1904,  1,  77. 


METABOLISM    IN   FEVER  505 

METABOLISM  IN  FEVER  INDUCED  BY  SURRA  TRYPANOSOMES 


Period. 


I.  Normal  (average) 
II.  Inoculation     and 

prodromal 

III.   1st  of  fever 


a  2 

£  P 

5  < 

<  *j 

Qg 


IV.  2d  of  fever  (aver- 
age)      11-17 

V.  3d  of  fever  (aver- 
age)  '   18-20 

VI.  Final  period  (aver- 
age)  1   21-24 


Oi 


5-67 

5-67 
5-67 
5-67 
5-67 
5-67 

4-37 


+  O.15 

—0.18 
— 0.40 
— 0.46 
— 1.06 


-4-63 


58S 

58S 
S85 
58s 
585 
585 


348 


510.0 

469-3 
521.4 
556-9 
675-2 
729-3 

665.2 

665.0 


59-8 

58.3 
63-9 
68.2 
81.6 
88.9 

83.7 


?< 


1081 
1 1 54 
1388 
1507 

1404 


74.0     1218 
62.0       go7 


Body 
Temp. 


Max. 


39-4 
39-5 
39-6 
40.1 
39-2 


40.4 
38.8 


Min. 


38.3 
38.3 
37-7 
39-6 
37-9 


38.5 
35-5 


Long  before  these  experiments  Wood1  had  found  an  aver- 
age increase  of  23  per  cent,  (calculated  by  Welch)  in  the  heat 
production  of  fasting  dogs  after  inducing  fever;  and  he  also 
found  that  mere  ingestion  of  food  by  a  normal  dog  would  cause 
a  greater  heat  production  than  fever  itself. 

Traube,2  who  was  the  first  modern  scientific  clinician, 
attributed  the  cause  of  fever  to  a  cramp-like  constriction  of  the 
peripheral  arterioles,  which  prevented  the  proper  distribution 
of  the  blood  at  the  surface  and  therefore  hindered  the  normal 
cooling  of  the  body.  Since  Traube's  writings  on  the  subject 
were  published  the  cause  of  fever  has  been  attributed  not  to 
greater  heat  production,  but  to  a  disturbance  in  the  mechanism 
of  the  regulation  of  heat  loss.  On  recalling  the  fact  that  the 
metabolism  of  a  fasting  dog  may  be  raised  from  100  calories 
in  fasting  to  189  calories  after  giving  meat  (see  p.  234)  without 
any  change  of  body  temperature,  it  becomes  evident  that  the 
increased  heat  production  in  fever  cannot  alone  be  the  cause 
of  the  high  body  temperature.  In  fact,  as  has  already  been 
set  forth,  the  rise  in  the  body  temperature  from  failure  of  the 

MVood:   "Fever,"  Smithsonian  Contributions  to  Knowledge,  Washington, 


1880. 


810. 


2  Traube:  "Allgemeine  medizinische  Central-Zeitung,"  i863,xxxii,  410, 426, 


506  SCIENCE    OF    NUTRITION 

physical  regulation  may  of  itself  explain  the  increase  in  heat 
production. 

Senator1  early  recognized  that  the  increase  in  body  tem- 
perature took  place  in  consequence  of  a  disturbed  relation- 
ship between  an  abnormally  high  heat  production  and  a  heat 
elimination  not  correspondingly  high.  Senator  assumed  an 
increase  in  the  production  of  heat,  which  Traube  did  not, 
and  Leyden2  found  a  considerable  increase  of  metabolism  in 
fever. 

The  effect  of  a  cold  bath  upon  a  vigorous  man  is  to  constrict 
the  peripheral  blood-vessels  and  to  increase  the  heat  pro- 
duction. The  body  temperature,  instead  of  falling,  may  rise 
for  eight  or  ten  minutes  and  then  sink.3  If  the  individual  pass 
from  the  bath  during  the  earlier  minutes  the  hot  blood. comes 
to  the  surface  to  be  cooled,  and  the  body  glows  with  a  red  color, 
the  so-called  "reaction."  This  experiment  shows  that  there 
are  factors  invoked  during  the  first  few  minutes  which  prevent 
the  discharge  of  the  heat  produced.  One  factor  must  be  a 
general  constriction  of  the  peripheral  arteries,  causing  the 
blood  to  remain  in  the  heat-producing  inner  organs  of  the 
body.  In  this  experiment,  therefore,  cooling  of  the  organism 
is  prevented  by  the  mechanism  of  physical  regulation  above 
described,  and  the  mechanism  of  chemical  regulation  which 
renexly  increases  heat  production. 

To  combat  a  rise  in  temperature,  however,  the  only  means 
available  is  the  physical  regulation — i.  e.,  the  change  in  the 
distribution  of  the  blood  and  the  production  of  sweat.  If  these 
avenues  of  heat  loss  be  diminished  or  shut  off,  heat  accumulates 
within  the  body  and  the  temperature  rises.  Why  an  increase 
in  heat  production  of  89  per  cent,  may  not  cause  a  rise  in 
temperature  in  a  normal  animal  has  already  been  explained ; 
whereas,  a  high  fever  may  be  accompanied  by  much  less  of  an 
increase  in  metabolism.     The  cause  of  the  fever  must,  there- 

1  Senator:  "Allgemeine  medizinische  Central-Zeitung,"  1868,  xxxvii,  926; 
and  "Untersuchungen  liber  die  fieberhaften  Prozesse,"  Berlin,  1873. 

2  Leyden:  "Deutsches  Archiv  fur  klinische  Medizin,"  1870,  vii,  5,36. 

3  Lefevre,  J.:    "Comptes  rendus  soc.  biol.,"  1894,  xlvi,  604. 


METABOLISM   IN   FEVER  507 

fore,  be  a  diminution  in  the  ability  to  discharge  the  heat  pro- 
duced. 

In  further  support  of  this  Senator  has  shown  that  the 
fever  following  pus  injections  in  a  dog  begins  with  a  retention 
of  heat  within  his  body.  Nebelthau1  found  in  a  rabbit  that 
during  the  first  twelve  hours  of  infection  in  which  the  tem- 
perature rose  from  38. 6°  to  40.  i°  the  discharge  of  heat  was 
but  96.3  per  cent,  of  that  of  the  previous  period.  Assuming 
the  heat  production  to  have  been  the  same  in  these  two  pe- 
riods, then  the  retention  of  heat  would  account  for  the  patho- 
logic increase  in  temperature.  At  a  later  stage  the  discharge 
of  heat  rose  to  equalize  its  production  at  the  higher  temper- 
ature. 

It  .is  evident  from  this  discussion  that  a  problem  of  great 
interest  is  involved  in  the  following  three  questions:  (1)  Does 
an  increased  metabolism  precede  a  rise  in  body  temperature? 
(2)  Do  increases  in  metabolism  and  body  temperature  occur 
simultaneously?  (3)  Does  the  rise  in  body  temperature  pre- 
cede the  increase  in  metabolism?  The  questions  can  only  be 
answered  by  simultaneous  determinations  of  the  heat  produc- 
tion by  the  methods  of  direct  and  indirect  calorimetry,  ac- 
complished in  short  periods  and  using  most  exact  methods 
and  technic. 

Such  work  was  accomplished  by  Coleman  and  DuBois2 
in  their  studies  concerning  typhoid  fever.  Their  results  are 
presented  in  the  form  of  a  chart  (Fig.  26). 

In  every  one  of  these  cases  there  was  a  rising  body  temper- 
ature. In  every  case  but  one  an  increase  in  heat  production 
accompanied  the  rising  body  temperature;  and.  the  heat 
elimination,  though  not  equal  to  the  heat  production,  rose  to 
meet  the  needs  of  the  higher  level  of  metabolism.  The  major 
part  of  the  evidence,  therefore,  points  to  an  increase  in  the 
metabolism  which  is  coincident  with  an  elevation  of  body 
temperature  when  determinations  are  made  in  hourly  periods. 

1  Nebelthau:    "Zeitschrift  fur  Biologie,"  1895,  xxxi,  353. 

2  Coleman  and  DuBois:   "Archives  of  Internal  Medicine,"  1915,  xv,  887. 


5o8 


SCIENCE    OF   NUTRITION 


In  one  instance  (Morris  S.,  October  24th)  the  heat  production 
and  heat  elimination  both  fell  notwithstanding  a  rising  body 


Edward   B 

Nov    6 


Hr 
40C 
39.6 
39  2 
388 

Cal 

90 
80 
70 


John  K      Morris  S 

Dec  15  OCT  24 


Morris  S 

Nov   18 


-L 

2 

3 

1 

? 

1 

z 

3 

_L 

? 

SI 

^ .^ 

lift 

It 

_  £ 

■v 

/ 

-  1 

1 

^j, 

„• 

\ 

HF, 

,1 

h 

'R 

OL 

•■ 

■ 

^ 

^ 

HE" 

M 

F 

'I 

If 

t: 

•1 

- 

■ 

^^ 

■-- 

-^- 

'• 

MORRlS    S. 
Nov     17 


MORRIS    S. 
Dec     20 


MORRIS     S. 
Dec    21 


HR 

•C 

39i6 
39.2 
38.8 
38.4 

380 

Cal 
80 

70 

60 


Fig.  26. — Curves  showing  the  relationship  and  heat  elimination  in  fever 
Rising  temperature.  The  uppermost  line  shows  the  rectal  temperature  as 
measured  every  twenty  minutes.  The  heavy  continued  line  represents  the  heat 
production  in  hourly  periods  as  determined  by  the  method  of  indirect  calorim- 
etry.  The  dotted  line  gives  the  heat  elimination  as  determined  by  the  meas- 
urement of  the  calories  of  radiation,  conduction,  and  vaporization.  The  differ- 
ence between  the  levels  of  these  two  lines  represents  the  heat  stored  in  the  body 
as  the  temperature  rises.  Note  the  fact  that  in  every  case  except  one  the  heat 
elimination  increases  with  a  rising  temperature. 


1 

? 

7i 

1 

? 

?i 

1 

? 

-^ 

y 

. 

f- 

1— 1 — 

4 

' 

.. 

.. 

- 

- 

— 

/ 

r 

. 

.. 

■■ 

•• 

■- 

- 

temperature.     This    could    only    have    been    accomplished 
through  an  alteration  in  the  apparatus  for  the  elimination  of 


METABOLISM   IN   FEVER  509 

heat  from  the  body,  in  the  sense  of  Traube's  analysis  of 
fever. 

Coleman  and  DuBois  also  cite  experiments  which  show  that 
when  the  body  temperature  is  constant  in  high  fever  the  heat 
production  and  heat  elimination  are  equal  to  each  other,  and 
when  the  body  temperature  falls  the  heat  elimination  rises 
above  the  heat  production,  while  the  amount  of  the  latter  may 
or  may  not  fall. 

Coleman,  Barr,  and  DuBois  have  recently  noted  in  the 
case  of  a  man  suffering  from  erysipelas  that  a  fall  in  body 
temperature  of  ic  C.  during  sleep  in  the  calorimeter  had  no 
effect  upon  the  hourly  production  of  heat  (unpublished).  In 
this  individual  the  reduction  of  body  temperature  was  there- 
fore wholly  dependent  on  the  mechanism  of  the  physical  reg- 
ulation of  temperature. 

On  the  whole,  these  experiments  show  that  in  fever  the  in- 
crease in  metabolism  and  of  body  temperature  occur  simul- 
taneously. Further  experiments  planned  along  these  lines, 
using  other  fevers  and  perhaps  even  shorter  periods,  will,  it 
is  hoped,  give  clearer  evidence  whether  there  is  any  reason 
for  an  increased  heat  production  other  than  a  rise  in  body 
temperature ;  or  whether  there  is  usually  a  preliminary  stimu- 
lus to  increased  metabolism  before  the  rise  in  body  tempera- 
ture occurs. 

Nebelthau  has  shown  a  fall  in  temperature  and  heat  pro- 
duction in  a  rabbit  whose  cord  was  divided  between  the  sixth 
and  seventh  cervical  vertebrae,  and  has  also  demonstrated  that 
under  these  circumstances  infection  with  erysipelas  of  the  pig 
had  no  influence  on  temperature  or  heat  production.  The 
inference  is  that  the  febrile  toxins  act  through  the  higher 
vasomotor  centers,  whose  regulatory  control  is  lost  in  the 
above  experiment. 

A  kindred  interpretation  may  be  placed  on  the  experiments 
of  Mendelson,1  who  was  unable  to  produce  fever  through  pus 
injections  when  the  dog  was  under  the  influence  of  chloral  or 

1  Mendelson:   "Yirchow's  Archiv,"  1885,  c,  274. 


5IO  SCIENCE   OF   NUTRITION 

morphin,  although  such  treatment  in  a  normal  animal  caused 
a  rise  in  temperature  of  from  36.30  to  39. 90  in  forty-five  min- 
utes. Mendelson  also  finds  a  constant  constriction  of  the 
renal  blood-vessels  in  fever. 

Further  experimentation  convinced  Sawadowski1  that  fever 
cannot  be  produced  after  the  mid-brain  has  been  severed 
from  the  medulla,  whereas  if  the  mid-brain  be  left  intact,  but 
the  cerebrum  be  sectioned  from  it,  fever  may  be  induced  in 
the  ordinary  course.  Citron  and  Leschke2  have  found  that 
destruction  of  the  median  portion  of  the  'tween  brain  on  the 
boundary  between  the  optic  thalamus  and  the  corpus  quadri- 
geminum  anterius,  the  "  'tween  brain  puncture,"  converts  a 
rabbit  into  the  equivalent  of  a  cold-blooded  animal.  Under 
these  circumstances  it  is  impossible  to  produce  infective  or 
non-infective  fevers  of  any  kind.  The  toxic  substance  must 
therefore  act  on  nerve-cells  in  the  mid-brain,  which,  in  turn, 
stimulate  the  medullary  centers. 

At  times  during  high  fever  the  skin  may  be  red  and  the 
peripheral  blood-vessels  distended.  Although  there  is  no 
sufficient  explanation  for  the  continuance  of  fever  when  the 
radiation  and  conduction  of  heat  from  the  surface  of  the  body 
are  thus  increased,  Krehl3  suggests  that  the  quantity  of  blood 
flowing  through  the  vessels  at  the  time  may  be  inadequate  to 
reduce  the  body's  temperature. 

The  second  means  of  physical  regulation  of  the  body  tem- 
perature is  through  the  evaporation  of  water  from  both  the 
lungs  and  the  sweat-glands.  It  might  be  surmised  that  the 
activity  of  this  mechanism  was  reduced  in  fever.  Nebelthau4 
has  shown  that  the  heat  lost  by  evaporation  of  water  and  by 
radiation  and  conduction  bear  exactly  the  same  ratio  to  each 
other  in  normal  and  in  fever-infected  rabbits.  Since  Rubner 
(p.  140)  has  proved  that  the  elimination  of  water  in  normal 

1  Sawadowsky:  "Centralblatt  fiir  medizinische  Wissenschaft,"  1888,  xxvi, 
161. 

2  Citron  and  Leschke:  "Zeitschrift  fiir  ex.  Path,  und  Ther.,"  1913,  xiv,  379. 

3  Krehl:    "Pathologische  Physiologie,"  1904,  p.  453. 

4  Nebelthau:    Loc.  cit. 


METABOLISM   IN   FEVER  51I 

animals  greatly  increases  at  high  temperatures,  the  mere 
maintenance  of  the  usual  water  evaporation  during  fever  would 
of  itself  be  abnormal. 

Lang1  has  shown  that  the  elimination  of  sweat  is  reduced 
during  the  rise  of  temperature  in  man,  but  at  the  height  of 
fever  is  the  same  as  the  normal,  while  there  is  some  increased 
evaporation  from  the  lungs.  He  has  also  shown  that  the  se- 
cretion of  sweat  is  increased  50  per  cent,  after  the  ingestion 
of  food  as  against  an  increase  of  70  per  cent,  in  the  normal 
individual. 

Recent  experiments  by  Schwenkenbecker  and  Inagaki2 
show  that  the  "insensible  perspiration"  in  fever  is  as  great  as 
in  health,  and  that  although  the  urine  may  decrease  in  quan- 
tity there  is  no  actual  accumulation  of  water  in  the  body  as  was 
believed  by  von  Leyden  (see  p.  522). 

Calculations  made  by  Soderstrom3  from  the  work  of  Cole- 
man and  DuBois  show  that  in  typhoid  fever,  when  the  body 
temperature  is  rising,  the  heat  lost  by  water  vaporization 
through  the  skin  and  lungs  bears  a  lesser  relation  to  the 
total  heat  elimination  than  occurs  in  normal  individuals. 
On  the  contrary,  a  fall  in  body  temperature  is  accompanied 
by  a  relative  increase  in  the  water  elimination.  These  ex- 
periments confirm  the  ideas  of  von  Leyden,4  which  were  pub- 
lished in  1868. 

The  production  of  heat  in  fever  may  be  greatly  increased 
during  a  chill,  and  a  rapid  rise  in  temperature  may  follow. 
This  was  shown  by  Liebermeister5  in  a  case  of  malaria.  The 
temperature  rose  from  36. 90  in  the  first  half-hour  to  39. 50  at  the 
end  of  another  hour,  while  the  carbon  dioxid  expired  rose  from 
14.85  grams  to  34.20  grams  per  half-hour.  Barr,  Cecil,  and 
Du  Bois  (unpublished  experiments  of  191 7)  have  found  that 
during  the  chill  in  malaria  or  the  chill  following  intravenous 

1  Lang:   "Deutsches  Archiv  fur  klinische  Medizin,"  1904,  lxxix,  343. 

2  Schwenkenbecker  and  Inagaki:  "Archiv  fur  ex.  Path,  und  Pharm.,"  1906, 
liv,  168. 

8  Soderstrom :   Unpublished 

4  von  Leyden:  "Deutsches  Archiv  fur  klinische  Medizin,"  1869,  v,  273. 

6  Liebermeister:  Ibid.,  1871,  viii,  153. 


512  SCIENCE    OF    NUTRITION 

injection  of  typhoid  vaccine  the  extra  heat  produced  was  re- 
tained in  the  body,  causing  the  sudden  rise  in  body  temper- 
ature. The  amount  and  manner  of  heat  loss  was  essentially 
unchanged  from  level  of  the  previous  normal,  suggesting  that 
the  heat  retention  was  due  to  a  failure  of  the  vasodilator  sys- 
tem to  respond  normally.  The  chill  ensued  even  when  a  pa- 
tient was  surrounded  with  hot-water-bags  at  a  temperature  of 
420  C,  indicating  that  the  phenomenon  was  not  due  to  the 
mechanism  of  chemical  regulation  as  held  by  Krehl.1 

Infectious  fevers  are  characterized  by  a  toxic  destruction  of 
body  protein.  Sometimes,  as  in  the  earlier  stages  of  tuber- 
culosis, this  tissue  destruction  may  be  present  in  the  absence  of 
fever  itself.  Such  a  toxic  action  on  body  protein  is  also  ob- 
served in  cancerous  cases,  as  was  described  by  Fr.  Muller.2 
He  writes:  "In  the  7  cases  (of  carcinoma)  cited,  the  ni- 
trogen excretion  was  larger  than  the  nitrogen  ingestion,  and 
consequently  the  body  lost  protein.  In  2  cases  the  protein 
loss  was  no  greater  than  in  healthy  individuals  with  similar 
insufficient  nourishment.  In  all  the  other  cases  the  protein 
metabolism  was  decidedly  above  that  of  healthy  men  under  the 
same  conditions.  Even  an  ample  dietary  was  not  able  to  es- 
tablish nitrogen  equilibrium.  As  more  food  was  given  the 
nitrogen  elimination  rose  higher  and  higher,  but  the  point  of 
nitrogen  equilibrium  seemed  unattainable."  Muller  compared 
the  cachexia  of  carcinoma  with  that  found  in  febrile  processes 
and  believed  them  to  be  analogous. 

Under  these  conditions  the  heat  production  may  be  in- 
creased 30  or  40  per  cent,  above  the  normal,  despite  the  char- 
acteristic cachexia.3  In  milder  cases  of  carcinoma,  however, 
an  increase  in  metabolism  is  not  apparent.4 

As  regards  tuberculosis  May5  writes:  "Larger  quantities  of 
the  toxins  produce,  with  certain  exceptions,  a  direct  injury  to 

1  Krehl:    "Pathologische  Physiologie,"  1904,  p.  452. 

2  Muller,  F.:    "Zeitschrift  fur  klinische  Medizin,"  1889,  xvi,  496. 

3  Wallersteiner:  "Deutsches  Archiv  fur  klinische  Medizin,"  1914,  cxvi,  145. 

4  Magnus-Levy:    "Zeitschrift  fur  klinische  Medizin,"  1906,  lx,  177. 

5  May:  OttV'ChemischePathologiederTuberculose,"  Berlin,  1903,  p.  335. 


METABOLISM   IN   FEVER  513 

the  cell  protoplasm.  They  are  strongly  toxic.  The  quantity 
of  protein  destruction  attributable  to  this  cause  is  not  very 
large  and  becomes  of  importance  only  when  continued  for  a 
long  period  of  time  and  where  there  is  no  compensatory  regen- 
eration. It  appears  that  the  power  to  regenerate  on  the  part 
of  these  cells  which  are  destroyed  by  toxins  is  greatly  reduced 
and  in  severe  cases  entirely  lost." 

Other  fevers  show  a  high  toxic  destruction  of  protein. 
F.  Miiller1  reports  a  daily  loss  of  10.8  grams  of  nitrogen  (equal 
to  318  grams  of  muscle)  by  a  typhoid  patient  during  eight  days 
of  fever  when  the  daily  food  contained  8.3  grams  of  protein 
nitrogen  and  about  1000  calories.  Administration  of  antipy- 
rin  which  lowered  the  body  temperature  somewhat  lessened  the 
protein  destruction.  During  fever  in  croupous  pneumonia 
the  protein  metabolism  is  much  higher  than  normal.  After 
the  crisis  there  is  still  a  large  excretion  of  nitrogen  in  the  urine 
which  continues  until  the  croupous  exudate  has  been  decom- 
posed by  autolysis,  absorbed  by  the  blood,  and  metabolized  in 
the  body  (epicritical  nitrogen  elimination).  In  acute  pneu- 
monic phthisis  (galloping  consumption) ,  with  its  caseous  trans- 
formation of  lung  tissue,  there  is  a  very  high  waste  of  tissue 
protein.  F.  Miiller2  has  shown  that  while  the  croupous  exu- 
date readily  undergoes  autolysis  at  a  temperature  of  400,  with 
the  production  of  deutero-albumoses,  lysin,  leucin,  tyrosin, 
etc.,  the  caseous  mass  does  not  undergo  autolysis,  although  it 
permits  free  diffusion  of  soluble  material,  such  as  phosphates. 
Hence,  although  the  protein  of  the  cheesy  mass  is  insoluble 
in  the  organism,  the  soluble  toxins  may  be  absorbed  from  the 
diseased  part,  and  be  the  causative  agent  of  the  rapid  destruc- 
tion of  body  protein  in  galloping  consumption. 

The  toxic  destruction  of  protein  in  infective  fever  was 
definitely  established  by  Kocher,3  who  found  that  after  giving 
to  a  typhoid  patient  a  diet  containing  carbohydrate  in  large 

1  Miiller,  F.:   "Centralblatt  fur  klinische  Medizin,"  1884,  v,  569. 

2  Miiller,  F.:  "Verhandlungen  des  2oteH  Congresses  fur  innere  Medizin," 
1902,  section  iv,  p.  192. 

3  Kocher:  "Deutsches  Archiv  fur  klinische  Medizin,"  1914,  cxv,  106. 

33 


5H 


SCIENCE   OF   NUTRITION 


amount  and  containing  very  little  protein  it  was  absolutely 
impossible  during  the  febrile  period  to  reduce  the  output  of 
urinary  nitrogen  to  that  corresponding  to  the  low  level  of  the 
normal  "wear  and  tear"  quota  of  protein  metabolism.  With 
the  decrease  in  the  intensity  of  the  febrile  process  the  loss  of 
body  nitrogen  gradually  diminished.  This  appears  in.  the 
following  table: 

PROTEIN  METABOLISM   IN  TYPHOID   FEVER 

Weight,  57.5  to  59.8  kgm. 


Food. 

N  IN 

Excreta. 

N 
Loss. 

Uric 
Acid,  Gm. 

Day  of  Fever. 

Temp. 

Cal. 

N. 

Cal.  per 
Kg. 

10 

3448 

4-7 

60 

21.09 

-16.39 

1.38 

39-2° 

11 

3335 

4-7 

58 

18.35 

-13-75 

1.26 

39-3° 

12 

3213 

2.2 

50 

39-3° 

13 

3213 

2.2 

56 

16.9 

-14.7 

°-93 

38.750 

14 

3213 

2.2 

56 

16.46 

—  14.26 

1.23 

38-7° 

15 

3213 

2.2 

56 

15-4 

-13-2 

I.OI 

38.45° 

16 

3213 

2.2 

,S6 

10.4 

-8.2 

0.68 

37-3° 

17 

3213 

2.2 

56 

5-76 

-3-56 

0.58 

37-6° 

18 

4666 

3-5 

78 

6.70 

-3.20 

0.61 

38.1  ° 

J9 

4666 

3-5 

7« 

6.79 

-3-2Q 

o.45 

37-i° 

20 

4666 

3-5 

78 

5-Si 

-2.31 

0.41 

Normal. 

21 

4666 

3-5 

78 

5-93 

-2.43 

0.26 

Normal. 

Daily  creatinin  reduced  from  2.5  to  1.5  grams. 

Although  the  nitrogen  in  the  urine  of  a  normal  man  when  this 
diet  is  given  ranges  between  2.5  to  4  grams,  during  the  febrile 
period  of  this  typhoid  patient  it  averaged  16  grams  and  even 
reached  20  grams  per  day.  Creatinin,  uric  acid,  sulphur,  and 
phosphorus  elimination  were  increased  during  the  febrile 
period,  but  declined  with  the  decline  in  protein  metabolism. 
Coleman  and  DuBois1  gave  to  typhoid  patients  diets  which 
contained  much  larger  quantities  of  protein  (as  much  as  16 
grams  of  nitrogen  daily),  but  they  were  unable  to  obtain  nitro- 
gen equilibrium,  even  though  the  diet  was  rich  in  carbohydrate. 
The  following  table  gives  a  summary  of  their  data: 


1  Coleman  and  DuBois:   ".\rchives  of  Internal  Medicine,"  1915,  xv, 


METABOLISM   IN   FEVER 


515 


CHART  SHOWING  NEGATIVE  NITROGEN  BALANCES  IN  TY- 
PHOID PATIENTS  WHO  RECEIVE  FOOD  CALORIES  IN  EX- 
CESS OF  CALCULATED  HEAT  PRODUCTION.  RESULTS  ARE 
AVERAGES   PER   DAY 


Patient. 


Morris  S.. 

Charles  F. 
KarlS.... 

John  K..  . 
Frank  W. 


Dates  or  Days 

Days 

of  Disease, 

in 

Inclusive. 

Period. 

Oct.  23- 

Nov.  3 

12 

Dec.  19-24 

6 

Nov.  28-30 

3 

Jan.  12-18 

7 

Jan.  19-22 

4 

Jan.  15-20 

6 

Days  of  Disease. 

II-T4 

4 

15-19 

5 

20-23 

4 

Calcu- 

Range of 

Maximum 

Temperature, 

Degrees  F. 

lated 
Heat 
Pro- 
duction, 
Cal. 

Food 
Calo- 
ries. 

Food 
N, 
Gm. 

102.8-104.6 
IOI.9-105.1 

2266 
2085 

2863 
2989 

16.4 
13.2 

101. 2-103.4 

I752 

245* 

12.0 

101. 0-105.0 
98.8-  99.0 

2197 
1678 

.  29»5 
2819 

16.1 
14.6 

103. 2-104.0 

2568 

104. 0-105. 4 

2200 

2250 

"•3 

103.0-104.0 

2238 

3320 

15-3 

101.0-103.6 

2054 

2362 

15-9 

Nitrogen 

Balance, 

Gm. 


-4.4 


■4.6 
•3-2 
■1.9 


■S-o 

-3-3 
1-5 


Coleman  and  DuBois  conclude  that,  though  there  was 
ample  protein  in  the  diet  to  establish  nitrogen  equilibrium  in 
the  normal  man,  it  could  not  accomplish  this  in  typhoid  fever. 
It  was  impossible  to  escape  the  conclusion  that  the  destruc- 
tion of  protein  is  caused  by  the  toxins  of  the  disease.  In  some 
cases  the  protein  destruction  continued  several  days  after 
the  body  temperature  had  reached  a  low  level. 

In  all  fevers  the  septic  products  act  upon  the  hunger  cen- 
ters in  the  brain,  and  appetite  is  wanting.  This  is  evidenced 
throughout  the  course  of  tuberculosis,  for  example,  and  tends  in 
this  case  to  weaken  the  body's  resistance  through  undernutri- 
tion.    Forced  feeding  is  therefore  resorted  to. 

The  experiments  of  von  Hosslin1  strongly  affirmed  the  be- 
neficence of  a  liberal  diet  in  ordinary  fevers.  He  writes:  "The 
results  show  that  febrile  patients,  or  at  least  those  who  do  not 
run  temperatures  above  400  to  40. 50,  can  digest  and  absorb 
the  total  amount  of  protein,  fat,  and  carbohydrates  which  can 
be  given  them  with  their  diminished  appetite,  provided  the 


1  von  Hosslin:    "Virchow's  Archiv,"  1882,  lxxxix,  317. 


5i6 


SCIENCE    OF   NUTRITION 


food  is  administered  in  a  proper  form.  Temperature  and 
metabolism  are  only  slightly  increased  thereby." 

The  efficiency  of  a  carbohydrate  diet  in  typhoid  fever  was 
first  demonstrated  by  Shaffer  and  Coleman,1  who  showed  that 
the  ingestion  of  large  amounts  of  carbohydrate  in  a  medium 
protein  diet  may  almost  maintain  the  patient  in  nitrogen 
equilibrium  throughout  the  disease.  The  diet  consisted  of 
milk,  milk-sugar,  diluted  cream,  eggs,  and  sometimes  arrow- 
root starch.  Shaffer  writes:  "It  was  only  when  we  gave  60, 
70,  or  even  80  calories  per  kilogram  of  body  weight — between 
3000  and  4000  calories — that  the  greatest  sparing  was  ob- 
served." 

The  results  obtained  from  two  individuals  suffering  from 
typhoid  are  presented  in  the  following  table : 


INFLUENCE    OF   CARBOHYDRATES   ON  PROTEIN  METABOLISM 
IN  TYPHOID   FEVER 
Subject  I. 


No.  of 
Days  in 
Period. 

Range  of  Maxi- 
mum Temp. 
During  Period. 

Total 
Calo- 
ries of 
Food. 

Calories 
per  Kg. 

Nitrogen 
in  Food. 

Nitrogen 
to  Body. 

Period. 

Total. 

From 
car- 
bohy- 
drates. 

I 

II 

Ill 

4 
6 

4 
8 
6 
4 

104    -103.2°  F. 
103.6-102.8°  F. 
103.8-103.4°  F. 
io4.8-ioi.4°F. 
100.8-99. 40  F. 
Normal. 

4280 
5200 
2750 
5340 
4990 
2430 

72 
85 
45 
89 
83 
4i 

4S.0 
48.O 

7.0 
52.O 
48.O 

7.0 

13-9 
15.0 
15.0 

14.5 
13.8 

13-5 

-  0.9 

-  0.2 

-  8.5 

-  2.8 
+   1.2 

IV 

V 

VI... . 

-  0.3 

Subject  II. 


I. 

II. 

III. 

IV. 


104.4-102.6°  F. 

1920 

31 

7-8 

12.6 

102.8-100.6°  F. 

4290 

70 

47.0 

12.6 

Normal. 

1930 

32 

8.0 

12.7 

102.8-99.6°  F. 

4800 

78 

50.0 

14.1 

Relapse. 

Normal   conva- 

lescence. 

2460 

39 

12.0 

14.6 

-H-3 

—  1.1 

-  3-8 
+  3-6 


+  1.8 


*  Average  for  last  three  days  of  diet. 

1  Shaffer:    "Journal  of  the  American  Medical  Association,"  1908,  li,  974; 
Shaffer  and  Coleman,  "Archives  of  Internal  Medicine,"  1909,  iv,  538. 


METABOLISM   IN   FEVER 


5J7 


From  this  it  may  be  concluded  that  nitrogen  equilibrium 
may  be  very  nearly  maintained  throughout  the  course  of  ty- 
phoid fever  on  a  diet  containing  12  to  15  grams  of  nitrogen, 
provided  an  excess  of  carbohydrate  beyond  the  requirement  of 
the  organism  be  also  administered.  Very  likely  under  these 
circumstances  the  fat  in  the  diet  is  without  influence,  except 
that  it  is  retained  in  the  organism.  Upon  this  basis  rests  the 
very  notable  advance  achieved  by  the  Coleman-Shaffer 
"high  calorie  diet." 

Pioneer  work  with  accurate  technic  upon  the  subject  of 
the  respiratory  metabolism  in  typhoid  fever  was  first  ac- 
complished by  Kraus,1  Grafe,2  Roily,3  and  Coleman  and 
DuBois,4  but  the  most  complete  work  upon  the  subject  is 
presented  in  the  calorimeter  studies  of  Coleman  and  DuBois 
which  have  already  been  incidentally  alluded  to.  These 
authors  give  the  following  table  which  shows'  the  corre- 
spondence between  direct  and  indirect  calorimetry  obtained 
with  patients  suffering  from  typhoid: 


Total  calories  measured  in  all  experi- 
ments  

Excluding  first  periods 

Calories  measured  in  febrile  experi- 
ments excluding  all  first  periods. 


Indirect. 


12,822.03 
8,470.93 

5,720.21 


12,539-67 
8,488.97 

S,583-S5 


Divergence. 


Per  cent. 
—  2.2 
+0.2 

-2.4 


Ten  individuals  were  investigated.  Metabolism  records 
were  obtained  on  sixty-five  days.  Twenty-four  of  these  were 
devoted  to  the  study  of  Morris  S.,  a  patient  whose  metabolism 
was  determined  through  the  course  of  the  fever  and  two  re- 
lapses, and  one  year  later  when  he  returned  to  the  hospital 
in  perfectly  normal  health.     This  gave  the  opportunity  of 


1  Kraus:    "Zeitschrift  fur  klin.  Med.,"  1891,  xviii,  160. 

2  Grafe:   "Deutsches  Archiv  fur  klin.  Med.,"  191 1,  ci,  209. 

3  Roily:   Ibid.,  191 1,  ciii,  93. 

4  Coleman  and  DuBois:    "Archives  of  Internal  Medicine,"  1914,  xiv, 


5*8 


SCIENCE    OF   NUTRITION 


contrasting  the  effect  of  the  specific  dynamic  action  of  pro- 
tein in  the  same  individual  in  fever  and  in  health. 

Coleman  and  DuBois  state  that  the  average  increase  in  the 
basal  metabolism  in  typhoid  fever  is  approximately  40  per  cent., 
although  figures  of  over  50  per  cent,  are  frequently  encountered. 
The  following  table  shows  the  average  results  obtained  during 
the  various  weeks  of  typhoid  fever: 


BASAL    METABOLISM, 


ACCORDING   TO    PERIODS    OF   TYPHOID 
FEVER 


Periods. 

Number 
of 

Patients. 

Number  of 
Observa- 
tions. 

Average 

Per  Cent. 

Rise  Above 

Average 

Normal 

34.7  Calories 

per  Sq.  M. 

Average 

Respiratory 

Quotient. 

Ascending  temperature. .  .  . 
Continued  temperature. . . . 
Early  steep  curve 

2 
5 
3 
3 

2 
2 

2 
I 

3 
3 

1 
2 

2 

7 
4 
3 

3 
2 

4 
1 

4 

5 
1 
2 
2 

+37 
+42 
+  26 
+  16 

+  25 
+51 
+36 
+  16 

—    2 
+  6 

+  17 
+  iS 
+  4 

0.79 
0.77 
0.82 

0.82 

Relapse — 

Ascending  temperature. . 

Continued  temperature. . 

Early  steep  curve 

Late  steep  curve 

Convalescence — 

First  week 

Second  week 

Third  week 

0.82 
0.76 
0.78 
0.79 

0.91 
0.88 
0.S1 

Fourth  week 

Fifth  week 

0.86 
0.81 

The  considerable  increase  in  metabolism  during  the 
second,  third,  and  fourth  weeks  of  convalescence  is  a  note- 
worthy discovery.  It  is  during  this  period  that  a  regenera- 
tion of  body  protein  takes  place,  and  DuBois  points  out  that 
the  heightened  metabolism  is  reminiscent  of  the  increased  heat 
production  during  the  period  of  growth. 

The  specific  dynamic  action  of  food  administered  in  typhoid 
fever  was  found  to  be  almost  negligible,  although  during  con- 
valescence it  was  as  high  as  in  normal  individuals.  The 
following  table  shows  these  results: 


METABOLISM   IN   FEVER 


519 


SPECIFIC  DYNAMIC  ACTION  OF  PROTEIN  AND  CARBOHYDRATE 
IN    HEALTH,    FEVER,    AND    CONVALESCENCE 


Subjects. 

Number  of 
Experi- 
ments. 

Average 

Gm.  of 

Nitrogen  or 

Glucose  in 
Food. 

Average 
Gm.  Food 
per  Kg. 
Body  Weight 
Nitrogen  or 
Glucose. 

Average 

Per  Cent. 

Rise  in 

Metabolism. 

Protein  meal. 

Two  normal  men* 

2 

10. 1 

0.147 

9-3 

Four  febrile  patients . .  . 

6 

8.6 

O.I74 

4-5 

Four  convalescents .... 

5 

10.2 

0.217 

16.6 

Commercial  glucose. 

Three  normal  men*.  .  . 

3 

115.0 

1.6 

9.1 

Two  febrile  patients .  .  . 

4 

115-0 

2.2 

1.0 

Three  convalescents. .. . 

3 

115-° 

2.7 

9.8 

*  Since  the  completion  of  Paper  4  two  more  normal  controls  have  been  given 
the  test-meals.  Morris  S.,  on  Dec.  18,  1914,  showed  a  rise  of  6.5  per  cent,  after 
a  meal  containing  9.6  gm.  N.;  .Albert  G.,  on  Jan.  6,  1915,  showed  an  increase  of 
9  per  cent,  in  his  metabolism  after  115  gm.  commercial  glucose. 


The  meal  containing  protein  was  as  large  as  the  patient 
could  be  persuaded  to  take.  The  results  of  the  ingestion  of 
large  amounts  of  food  caused  only  a  slight  increase  in  the  basal 
metabolism  during  fever,  one  of  5  per  cent,  in  the  case  of  pro- 
tein and  only  1  per  cent,  in  the  case  of  commercial  glucose. 
The  ancient  doctrine  of  "starving  a  fever"  herewith  falls  to 
the  ground. 

The  effect  of  bodily  activity  upon  the  basal  metabolism 
does  not  appear  to  be  as  marked  during  typhoid  fever  as  in 
health.  Thus,  Coleman  and  DuBois  describe  how  Morris  S. 
was  quiet  during  a  first  hour,  was  restless  and  tossed  about 
the  bed  during  a  second  hour,  and  during  a  third  hour  was  evi- 
dently irrational,  tossed  about,  wrote  several  long  notes  which 
he  held  up  to  the  calorimeter  window,  telling  of  animals  that 
were  biting  him  with  their  sharp  teeth.  Yet  his  metabolism, 
which  was  43  per  cent,  above  the  normal  for  the  three-hour 
period,  was  only  5  per  cent,  higher  than  during  a  quiet  period 
of  observation  of  the  basal  metabolism  made  twro  days  later 
when  the  body  temperature  was  lower. 


5  20 


SCIENCE   OF   NUTRITION 


The  principal  cause  of  the  increased  metabolism  in  typhoid 
fever  lies,  therefore,  in  the  febrile  process  itself,  and  food  and 
restlessness  have  little  influence. 

The  respiratory  quotients  were  normal,  the  lowest  being 
0.72,  obtained  during  fasting,  and  the  highest  1.04,  obtained 
after  carbohydrate  ingestion. 

The  large  quantities  of  food  administered  to  the  typhoid 
patients  in  the  "high  calorie  diet"  are  as  completely  absorbed 
as  they  would  be  in  health.1 

Only  a  resume  of  the  more  important  principles  involved 
can  be  attempted  in  this  book,  and  those  interested  in  the 
metabolism  of  typhoid  patients  are  referred  to  the  details  in 
the  original  communication  of  Coleman  and  DuBois. 

An  illustration  of  the  course  of  nitrogen  metabolism  in  a 
different  fever— namely,  pneumonia — may  also  be  taken  from 
von  Leyden  and  Klemperer.2    The  details  are  given  below: 


METABOLISM   IN 

PNEUMONIA 

Food. 

Excreta. 

Temp,  on 

Loss  OF 

Successive 

Body 

Days. 

Quantity  in 

Calo- 

N. 

Fat. 

Carbohy- 

Urine 

Feces 

Total 

N. 

Grams. 

ries. 

drates. 

N. 

N. 

N. 

40.8  (highest). 

2000  milk. 

1360 

10.6 

70 

90 

24.7 

0.9 

25.6 

iS-o 

40.9  (highest). 

2000  milk, 
150  cream, 
100  lactose. 

1980 

1 1.4 

85 

197 

22.8 

0.9 

23-7 

12.3 

41.2  at  12  m. 

2000  milk. 

1975 

10.6 

70 

240 

21.7 

0.9 

22.6 

12.0 

36.8  at  7  P.  m. 

1 50  lactose. 

37.3  (highest). 

2000  milk, 
200  cream. 

1612 

11. 7 

90 

99 

21.9 

1.1 

23.0 

H-3 

36.8  (highest). 

2000  milk, 
200  cream, 
2  eggs. 

1752 

13-7 

100 

99 

18.5 

1.1 

19.6 

5-9 

36.8  (highest). 

2000  milk, 
300  cream, 
4  eggs. 

2018 

17-3 

120 

104 

18.7 

1.1 

19.8 

2-5 

In  this  case  it  is  apparently  demonstrated  that  nitrogen 
equilibrium  cannot  be  obtained  during  high  fever,  and  also 
that  the  loss  of  body  nitrogen  does  not  cease  at  the  crisis,  but 

1  DuBois:  "Archives  of  Internal  Medicine,"  1912,  x,  177;  Coleman  and  Gep- 
hart:    Ibid.,  1915,  xv,  882. 

2  von  Leyden  and  Klemperer:  "Handbuch  der  Ernahrungstherapie,"  1904, 
Bd.  ii,  p.  345. 


METABOLISM   IN   FEVER  521 

rather  continues  on  account  of  the  epicritical  elimination  of 
nitrogen  derived  from  the  protein  of  the  croupous  exudate. 
During  the  time  of  this  epicritical  elimination  the  body  appears 
unable  to  add  new  protein  to  itself.  About  four  days  after  the 
crisis  true  convalescence  begins,  with  the  upbuilding  of  new 
protein  tissue. 

On  autopsy  of  patients  who  have  died  of  fevers,  parenchy- 
matous and  fatty  degenerations  of  the  organs  have  been  found. 
These  changes  have  been  ascribed  to  overheating  of  the  cells. 

Litten1  warmed  guinea-pigs  artificially  and  noted  fatty  but 
no  parenchymatous  degeneration  of  the  tissues.  The  space  in 
which  the  animals  were  kept  was,  however,  insufficiently  ven- 
tilated, and  the  fatty  change  might  have  been  caused  by 
dyspnea,  as  results  in  normal  animals  (p.  423). 

Naunyn2  observed  that  rabbits  might  be  artificially  warmed 
for  thirteen  days,  so  that  an  average  body  temperature  of  41. 50 
was  maintained  without  any  parenchymatous  or  fatty  degen- 
eration taking  place.  The  animals  were  supplied  with  ample 
food,  water,  and  a  sufficient  supply  of  air.  Naunyn  found 
that  the  red  blood-cells  of  rabbits  and  dogs  remained  intact 
even  at  a  body  temperature  of  420.  Welch3  noticed  fatty  but 
no  parenchymatous  change  in  the  tissues  of  rabbits  after  ex- 
posure to  high  temperature  for  at  least  a  week.  One  rabbit 
which  had  been  subjected  to  high  temperature  for  four  days 
was  inoculated  with  the  bacilli  of  the  swine  plague  and  died  in 
thirty-six  hours,  showing  extreme  fatty  changes  in  the  heart 
and  other  organs. 

Ziegler4  discovered  degenerative  changes,  both  parenchy- 
matous and  fatty,  on  artificially  warming  rabbits.  The  ex- 
periment was  continued  in  1  case  for  twenty-nine  days.  He 
found,  however,  a  great  reduction  (30  per  cent,  and  more)  in 
the  quantity  of  hemoglobin  in  his  rabbits.  It  may  well  be  a 
question  whether  the  fatty  change  noticed  in  the  liver  and 

1  Litten:    "Yirchow's  Archiv,"  1877,  lxx,  10. 

2  Naunyn:   "Archiv  fur  ex.  Path,  und  Pharm.,"  1884,  xviii,  49. 

3  Welch:   "Medical  News,"  1888,  Hi,  403. 

*  Ziegler:   "Kongress  fur  innere  Medizin,"  1895,  xiii,  345. 


522  SCIENCE   OF   NUTRITION 

muscles  was  not  due  to  anemia  instead  of  to  the  hyperthermia. 
Since  fatty  infiltration  is  known  to  be  caused  by  dyspnea,  which 
frequently  terminates  life  in  fever,  one  might  investigate  this 
subject  to  see  whether  parenchymatous  change  in  fever  is  not 
solely  due  to  the  toxins,  and  fatty  change  to  the  anaerobic 
cleavage  of  materials  in  the  cells,  which  always  induces  fatty 
infiltration  (p.  489). 

Rosenthal1  states  that  if  diphtheria  toxin  be  administered 
to  rabbits  the  liver  is  rendered  incapable  of  retaining  glyco- 
gen. There  is  hypoglycemia  except  following  glucose  admin- 
istration, when  a  hyperglycemia  greater  than  that  possible  in 
normal  animals  occurs. 

Ever  since  the  experiments  of  von  Leyden2  a  retention  of 
water  in  fever  has  been  assumed.  It  has  also  been  shown  that 
there  is  a  retention  of  sodium  chlorid  within  the  body.  The 
intimate  relation  between  the  retention  of  water  and  salt  has 
been  beautifully  demonstrated  by  Sandelowsky3  in  Liithje's 
clinic.  Thus,  during  the  period  of  high  fever  in  pneumonia  a 
gain  in  weight,  a  sodium  chlorid  retention,  and  a  dilution  of  the 
organic  contents  of  the  blood  usually  went  hand  in  hand. 
After  the  crisis,  however,  a  loss  in  weight,  a  loss  of  chlorid,  and 
a  greater  concentration  of  blood  resulted.  Similar  conditions 
were  found  in  scarlet  fever.4  Sandelowsky  observed  that  when 
sodium  chlorid  was  given  to  a  patient  convalescent  from 
pneumonia  it  was  not  so  readily  eliminated  by  the  kidney  as 
it  would  have  been  normally.  He  attributed  this  to  a  dis- 
turbed renal  condition  which  was  not  wholly  restored  to  the 
normal  after  the  crisis.  This  brought  about  sodium  chlorid 
retention,  which  in  turn  caused  water  retention,  that  the  nor- 
mal osmotic  conditions  might  be  preserved,  thus  accounting 
for  the  gain  in  body  weight  and  the  loss  in  the  concentration 
of  the  blood  in  fever. 

It  has  since  been  shown  that  failure  to  excrete  chlorid 

1  Rosenthal,  F.:    "Archiv  fur  ex.  Path,  und  Pharm.,"  1014,  lxxv,  99. 

2  von  Leyden:    "Deutsches  Archiv  fur  klin.  Med.,"  1869,  v,  273. 

3  Sandelowsky:   Ibid.,  1909,  xcvi,  445. 

4  Oppenheimer  and  Reiss:    Ibid.,  p.  464. 


METABOLISM    IN    FEVER  523 

during  the  acute  stage  of  the  disease  is  almost  always  associ- 
ated with  a  concentration  of  sodium  chlorid  in  the  blood- 
plasma  below  5.62  grams  per  liter,  which  is  the  normal  thresh- 
hold  value  of  excretion1  (see  p.  167).  Hence  the  retention 
of  sodium  chlorid  is  not  due  to  kidney  insufficiency. 

As  regards  the  etiology  of  fever,  various  attempts  have 
been  made  to  identify  a  single  factor  which  would  cause  the 
high  temperature. 

Krehl  and  Matthes2  find  that  human  urine  during  fever 
contains  an  increased  quantity  of  albumoses  which  have  been 
shown  to  possess  a  decidedly  toxic  action  when  introduced 
into  animals.  Klemperer3  denies  that  these  albumoses  have 
any  toxic  action,  and  asserts  that  the  results  were  due  to  im- 
purities in  preparation.  In  other  respects  the  urine  has  gen- 
erally been  found  to  be  of  normal  character.  Thus,  Mohr4 
finds  that  the  relation  C  to  N  in  the  urine  is  unchanged  from 
the  normal,  which  indicates  that  there  is  no  qualitative  change 
in  the  character  of  the  general  protein  metabolism 

However,  there  is  a  very  noteworthy  record  made  by  A.  R. 
Mandel5  that  the  rise  of  temperature  in  so-called  aseptic  or 
surgical  fevers  is  accompanied  by  a  large  increase  in  the  purin 
bases  in  the  urine  of  patients  fed  with  milk.  The  temperature 
rises  and  falls  with  the  quantity  of  purin  bases  eliminated. 
The  uric  acid  elimination  is  reduced.  These  relations  are 
illustrated  in  Fig.  27 — a  case  of  resection  of  the  knee-joint 
for  tubercular  arthritis.  The  temperatures  recorded  represent 
the  average  of  observations  made  every  three  hours  during 
the  day. 

Another  research  available  in  this  connection  is  that  of 
von  Jaksch,6  who  noted  that  the  purin  bodies  in  the  urine  of 

1  Snapper:  "Beutsches  Archiv  fur  klin.  Med.,"  1913,  cxi,  429;  McLean, 
"Journal  of  Experimental  Medicine,"  191 5,  xxii,  366. 

2  Krehl  and  Matthes:  "Deutsches  Archiv  fur  klinische  Medizin,"  1895, 
liv,  501. 

3  Klemperer:    "Naturforscherversammlung,"  1903,  2,  ii,  67. 

4  Mohr:    "Zeitschrift  fur  klinische  Medizin,"  1904,  lii,  371. 

5  Mandel:    "American  Journal  of  Physiology,"  1904,  x,  452. 

6  von  Jaksch:    "Zeitschrift  fiir  klinische  Medizin,"  1902,  xlvii,  1. 


5  24 


SCIENCE    OF   NUTRITION 


tuberculous  patients  may  increase  from  a  normal  equivalent 
of  4.4  per  cent,  of  the  total  nitrogen  excreted,  to  one  represent- 
ing 1 1.3,  or  even  17.39  Per  cent.  Also  Benjamin1  reports  a 
case  of  typhoid  where  the  urine  contained  the  large  quantity 
of  0.1  gram  of  purin  bases  with  0.54  gram  of  uric  acid.  Erben2 
and  Leathes3  report  that  the  output  of  uric  acid  is  always  in- 
creased during  high  fever.  Erben  also  finds  that  the  content 
of  the  urine  in  xanthin  bases  and  amino-acids  is  greatly  aug- 


TEMP.  F.  LEUCOCYTf  5 

101°  13,000 


Fig.  27. — Resection  of  knee-joint  for  tubercular  arthritis. 


mented  in  measles  and  chicken-pox ;  and  that  the  xanthin  bases 
are  also  increased,  though  to  a  lesser  extent,  in  scarlet  fever 
and  typhoid.  Mandel4  has  fed  monkeys  with  bananas  and 
xanthin  and  witnessed  a  rise  in  body  temperature,  and  has 
noticed  that  if  sodium  salicylate  be  given  at  the  same  time  no 

1  Benjamin:   "Salkowski's  Festschrift,"  1904,  p.  61. 

2  Erben:   "Zeitschrift  fur  Heilkunde,"  1904,  xxv,  33. 

3  Leathes:   "Journal  of  Physiology,"  1907,  xxxv,  205. 

4  Mandel:   "American  Journal  of  Physiology,"  1907,  xx,  439. 


METABOLISM   IN   FEVER  525 

rise  in  temperature  occurs.  Ott1  reports  that  guanin,  adenin, 
and  hypoxanthin  cause  an  elevation  of  temperature  in  rabbits, 
while  uric  acid  does  not. 

Mandel  believes  that  the  purin  bases  liberated  through  the 
toxic  destruction  of  tissue  may  play  a  considerable  part  in 
producing  the  temperatures  noted  in  fever.  It  is  evident  that 
the  use  of  purin-free  milk  instead  of  purin-containing  meat  has 
its  scientific  justification. 

It  would  indeed  be  a  most  striking  fact  if  it  should  be  found 
that  the  cause  of  the  febrile  temperature  lies  in  the  effect  of 
purin  bases  on  the  heat-regulating  apparatus  of  the  mid-brain 
acting  through  the  vasomotor  system.  Antipyretics  do  not 
lower  body  temperature  in  the  normal  organism  in  man.  Is 
their  action  merely  to  nullify  the  action  of  purin  bases  upon 
the  nerve-centers?  Future  research  alone  can  decide  this. 
Such  conjectures  indicate  the  extraordinary  field  which  lies 
open  to  the  investigator  in  clinical  medicine. 

1  Ott:   "The  Medical  Bulletin"  (Medico-Chir.  College),  October,  1907. 


CHAPTER  XIX 

PURIN  METABOLISM— GOUT 

Uric  acid  was  discovered  in  urinary  calculi  by  Scheele  in 
1776,  and  was  found  to  be  present  in  gouty  concretions  by  Wol- 
laston  in  1797.  It  has  since  been  the  subject  of  investigations 
almost  without  number,  and  of  theoretic  speculation  beyond 
that  of  any  other  chemical  substance  described  in  medical 
literature.  The  older  work  concerning  the  excretion  of  uric 
acid  is  almost  valueless  on  account  of  the  inadequacy  of  the 
chemical  methods  of  the  times.  Accurate  determinations  of 
uric  acid  date  from  the  introduction  of  a  new  method  of  anal- 
ysis by  Salkowski  in  1882;  and  of  allantoin  by  Wiechowski  in 
1908. 

The  newer  researches  are  also  based  on  more  exact  chemical 
knowledge  of  the  precursors  of  uric  acid.  Much  valuable  in- 
formation has  been  gathered  as  regards  the  normal  method  of 
production  of  uric  acid,  although  it  will  be  seen  that  on  the 
pathologic  side  there  is  little  beyond  the  conjectural  to  reward 
the  student. 

Emil  Fischer1  grouped  together  uric  acid,  hypoxanthin, 
xanthin,  adenin,  and  guanin  as  bodies  whose  varying  structure 
depended  upon  slight  changes  around  the  chemical  nucleus  of  a 
substance  called  purin.  Purin,  according  to  Fischer,  may 
occur  in  the  body,  but  on  account  of  its  ready  decomposa- 
bility,  has  not  been  discovered  there. 

The  relations  between  the  purin  bodies  may  be  judged  from 
the  following  formulae: 

Purin C5H4N4 

Hypoxanthin C6H4N4O 

Xanthin C5H4N402 

Uric  acid C5H4N4O3 

Adenin C6H3N4NH2 

Guanin CBH3N4ONH2 

Fischer:  "Berichte  der  deutschen  chemischen  Gesellschaft,"  1899,  xxxii, 
435- 

526 


PURIN   METABOLISM — GOUT  527 

Hypoxanthin,  xanthin,  and  uric  acid  are  respectively  mono-, 
di-,  and  tri-oxypurin.  Adenin  is  aminopurin,  and  guanin  is 
aminohypoxanthin.  It  is  evident  that  uric  acid  is  the  most 
highly  oxidized  product  of  the  series,  and  might  readily  arise 
from  the  oxidation  of  hypoxanthin  and  xanthin.  It  is  also  ap- 
parent that  by  supplanting  the  NH2  group  in  adenin  and 
guanin  by  O,  they  would  be  converted  into  hypoxanthin  and 
xanthin  respectively,  and  that  from  these  substances  uric  acid 
might  arise  through  oxidation. 

These  reactions  may  be  thus  expressed: 

HN— CO  HN CO  HN CO 

NH2— C     C— NH    ►        C  =  OC— NH    >        C  =  OC— NH 

\pn  Xfll  \m 

^CH  ||      /CH  ||       /CO 

N— C— N  HN C— N  HN C— NH 

Guanin,  Xanthin,  Uric  acid, 

amino-oxypurin.  dioxvpurin.  trioxypurin. 

T 
I 

N  =  CNH2  HN— CO 

II  II 

HC     C— NH     >    HC     C— NH 

/CH  ||      ||      /CH 

N— C— N  N— C— N 

Adenin,  Hypoxanthin, 

aminopurin.  oxypurin. 

The  deamination  of  guanin  and  adenin  is  accomplished  by 
hydrolysis  and  may  occur  in  the  absence  of  oxygen,  whereas  the 
conversion  of  hypoxanthin  into  xanthin  and  the  latter  into 
uric  acid  are  true  processes  of  oxidation. 

The  knowledge  of  the  hydrolytic  cleavage  products  of 
nucleic  acid  is  derived  largely  from  the  work  of  Kossel,1  who 
added  adenin,  cytosin,  and  thymin  to  chemical  literature. 

The  formula?  of  the  three  pyrimidin  bases — uracil,  cytosin, 
and  thymin — are  as  follows: 

HN— CO  N  =  CNH2  HN— CO 

OC     CH  OC     CH  OC     CCH3 

I      II  I       II  I      II 

HN— CH  HN— CH  HN— CH 

Uracil.  Cytosin.  Thymin. 

1  For  the  extensive  literature  on  this  subject  consult  the  valuable  mono- 
graph of  Walter  Jones,  "Nucleic  Acids,"  London,  1914. 


528  SCIENCE   OF   NUTRITION 

Kossel  and  Steudel1  point  out  the  fact  that  purin  bases 
contain  the  pyrimidin  nucleus,  and  that  cytosin,  for  example, 
needs  only  cyanic  acid,  CONH,  and  an  atom  of  oxygen  to 
convert  it  into  uric  acid. 

They  query  whether  the  pyrimidin  bases  are  precursors  or 
metabolized  products  of  the  purins,  but  the  question  is  still 
unsettled.2 

Mendel  and  Myers3  report  that  the  pyrimidin  bases,  when 
administered  intravenously  or  per  os,  reappear  in  the  urine 
unchanged  without  increasing  either  the  purin  or  the  urea 
output.  However,  when  nucleic  acids  containing  pyrimidin 
bases  are  administered,  the  bases  are  not  found  in  the  urine. 
The  pathway  of  their  disintegration  is  uncertain. 

Kossel's  work  presents  the  following  substances  as  charac- 
teristic cleavage  products  of  animal  and  vegetable  nucleic 

acids : 

Animal.  Vegetable. 

Thymus  nucleic  acid:  Yeast  nucleic  acid: 

Phosphoric  acid  Phosphoric  acid 

Guanin  Guanin 

Adenin  Adenin 

Cytosin  Cytosin 

Thymin  Uracil 

Hexose  Pentose 

Bang4  extracted  from  the  pancreas  a  nucleic  acid  containing 
phosphoric  acid,  a  pentose  and  guanin,  which  compound  he 
called  "guanylic  acid."  The  presence  of  a  pentose  in  animal 
nucleic  acid  is  an  anomaly.  Levene  and  Jacobs5  discovered 
the  formula  of  guanylic  acid,  and  solved  the  long-sought  prob- 

1  Kossel  and  Steudel:  "Zeitschrift  fur  physiologische  Chemie,"  1903, 
xxxviii,  49. 

2  Consult  Abderhalden:  "Lehrbuch  der  physiologischen  Chemie,"  1909,  p. 
381. 

3  Mendel  and  Myers,  V.  C:  "American  Journal  of  Physiology,"  1910,  xxvi, 

77- 

4  Bang:    "Zeitschrift  fur  physiologische  Chemie,"  1898-99,  xxvi,  133. 

5  Levene  and  Jacobs:  "Ber.  d.  d.  chem.  Ges.,"  1909,  xlii,  2469;  "Journal 
of  Biological  Chemistry,"  191 2,  xii,  421. 


PURIN   METABOLISM — GOUT  529 

lem  of  the  composition  of  nucleic  acid.  They  submitted 
guanylic  acid  to  neutral  hydrolysis  under  pressure,  which  re- 
moved phosphoric  acid  and  left  a  substance  (guanosin)  which 
readily  broke  up  on  acid  hydrolysis  into  d-ribose  and  guanin. 
These  two  hydrolyses  may  thus  be  written: 

HO\ 
0  =  PO— C^HgOs— C5H4N5O    +    H20    =    H3PO4    +    C6H904— C5H4N5O 

HO/  Guanylic  acid.  Guanosin. 

C5H9O4— C5H4N50     +     H20     =     C5H10O5     +     CsHsNjO 

Guanosin.  d-Ribose.  Guanin. 

Guanylic  acid  is  a  monobasic  nucleotid  which  yields  on 
cleavage  phosphoric  acid  and  the  nucleoside  guanosin. 

The  more  complicated  nucleic  acids  are  polymers  of 
nucleotids.  Thus,  Levene  and  Jacobs1  give  the  following 
formula  for  animal  nucleic  acid: 

HO\ 
O  =  PO— C6H10O4— C5H4N50 

/  Guanin  group. 

O 

HO\ 

O  =  PO— QHsOz— C5H5N2O2 
HO/  Thymin  group. 

o 

HO\ 

O  =  PO— CeHsOi— C4H4N30 
HO/  Cytosin  group. 

O 

\ 

O  =  PO— C6H10O4— C5H4N5 
HO/  Adenin  group. 

Levene  and  Medigreceanu2  found  that  animal  ferments 
have  the  power  of  hydrolytic  cleavage  over  nucleic  acid. 
Thus,  pancreatic  juice  or  intestinal  juice  through  nucleinase 
(1)  causes  the  resolution  of  a  polynucleotid  into  mononucleotids . 
Animal  tissues  were  also  found  to  contain  a  similar  ferment. 
Extracts  of  the  mucosa  of  the  intestine  contained  nucleotidase 

1  Levene  and  Jacobs:    "Journal  of  Biological  Chemistry,"  1912,  xii,  411. 

2  Levene  and  Medigreceanu:  Ibid.,  1911,  ix,  389. 

34 


530  SCIENCE   OF   NUTRITION 

(2)  which  splits  the  nucleotids  into  phosphoric  acid  and  nuclco- 
sids.  The  pyrimidin  nucleosids  are  not  further  acted  upon, 
but  the  purin  nucleosids  are  broken  up  by  nucleosidase  (3) 
into  their  constituent  carbohydrate  and  purin  groups.  The 
kidney,  heart  muscle,  and  liver  contain  all  the  above-named 
enzymes,  and  are,  therefore,  capable  of  demolishing  the  com- 
plex molecule  of  nucleic  acid. 

The  enzyme  nucleinase  which  breaks  the  polynucleotid 
complex  of  nucleic  acid  may  not  act  as  a  simple  unit.  Thus, 
Jones  and  Richards1  found  that  when  the  tetranucleotid,  yeast 
nucleic  acid,  was  mixed  with  pigs'  pancreas  it  is  split  into  two 
dinucleotids;  one  containing  the  guanin  and  cytosin  groups, 
the  other,  the  adenin  and  uracil  groups.  Not  only  this,  but 
Thannhauser2  found  that  after  digesting  yeast  nucleic  acid 
with  human  duodenal  juice,  the  nucleotid  containing  uracil 
was  split  off  and  there  remained  a  trinucleotid  containing 
guanin,  adenin,  and  cytosin.  Various  places  of  attack  are 
therefore  open. 

Selecting  the  nucleotids  forming  yeast  nucleic  acid,  one 
may  present  this  summary  of  their  transformation: 

Nucleotids  minus  H3PO4   =  Nucleosids  minus  d-ribose  =  Bases. 

Adenylic  acid >  Adenosin  >     Adenin 

Guanylic  acid  >  Guanosin  >     Guanin 

Cytodin-nucleotid >  Cytidin  >     Cytosin 

Uridin-nucleotid  >  Uridin  >     Uracil 

This  is  the  simplest  picture  of  the  transformations  which 
take  place.  Amberg  and  Jones3  have  shown  that  the  deamin- 
izing  enzymes  (see  p.  531)  may  convert  guanosin  into  xanthosin, 
which  yields  xanthin  on  hydrolysis,  or  convert  adenosin  into 
inosin,  which  yields  hypoxanthin  on  hydrolysis. 

Jones  ("Nucleic  Acids,"  p.  77)  presents  the  following 
scheme  of  the  methods  of  breakdown  of  a  guanin-adenin 
dinucleotid : 

1  Jones  and  Richards:   "Journal  of  Biological  Chemistry,"  1914,  xvii,  71. 

2  Thannhauser:  "Zeitschrift  fur  physiologische  Chemie,"  1914,  xci,  329; 
1915,  xcv,  259. 

3  Amberg  and  Jones:  Ibid.,  191 1,  lxxiii,  407. 


PURIN   METABOLISM — GOUT 


531 


ON 


5»4' 


OH 

o=p-o.c5H8o3.c5N4-oir 

0 

\  •» 

O=P-0.C5H8O3.C5^4-NH2 

OH 

Hucleic  Acid 


H^H2       C5H904.C6N4<0H2       CgHgO^CgS^jMjs       W^p 


Guanin    4- 


job 

c.HaH-oh 

Uric  Acid  4- 


*  OH 
C^H^OH 


Guanos in 


C5H904.C5N4:OH 
Xanthosin 


Inosin 


^Adenin 


c5h4h-^h 

Hypoxanthin 


Horbaczewski1  was  the  first  to  note  that  the  ingestion  of 
nucleoproteins  largely  increased  the  uric  acid  in  the  urine. 
Food  free  from  nucleoproteins  has  not  this  effect.  He  also 
found  that  if  fresh  spleen  pulp,  which  contains  no  uncombined 
purin  bases,  be  permitted  to  putrefy,  xanthin  and  hypoxan- 
thin made  their  appearance.  If  now  the  pulp  was  shaken  in 
the  air,  uric  acid  was  formed  from  the  oxidation  of  the  bases. 

Spitzer2  found  that  when  air  was  passed  through  aqueous 
extracts  of  spleen  and  liver  digested  at  400,  and  with  exclusion 
of  putrefaction,  uric  acid  was  produced.  The  quantity  of 
purin  bases  present  decreased  with  the  increased  formation 
of  uric  acid.  Purin  bases  added  to  such  a  digest  were  converted 
into  uric  acid,  hypoxanthin,  and  xanthin  readily  and  almost 
completely,  and  guanin  and  adenin  with  greater  difficulty. 
This  work  established  the  presence  of  oxidizing  enzymes,  the 

1  Horbaczewski :  "Sitzunjsberichte  der  Wiener  Academie  der  Wissen- 
schaft,"  1891,  c,  Abth.  iii,  p.  13. 

2  Spitzer:    "Pfliiger's  Archiv,"  1899,  lxxvi,  192. 


532  SCIENCE    OF   NUTRITION 

xanthin  oxidases,  which  could  act  on  the  purin  bases  in  the 
organism,  converting  them  into  uric  acid. 

Minkowski1  has  shown  that  if  a  man  be  given  hypoxanthin 
the  quantity  of  uric  acid  increases  in  his  urine.  He  also  showed 
that  if  a  man  ingest  thymus  gland,  the  nuclein  of  which  yields 
principally  adenin,  the  amount  of  uric  acid  is  increased  in  the 
urine.  If  the  thymus  be  given  to  a  dog,  the  uric  acid  plus 
allantoin  elimination  is  increased.  Allantoin  is  an  oxidation 
product  of  uric  acid  more  frequently  found  in  dogs'  than  in 
human  urine.  Minkowski  discovered  finally  that  adenin 
when  administered  to  a  dog  did  not  increase  the  uric  acid 
elimination,  and  was  not  excreted  as  such,  but  on  autopsy  of 
the  dog  the  uriniferous  tubules  were  found  to  contain  crystals 
the  chemical  structure  of  which  showed  them  to  be  aminodi- 
oxypurin.  In  other  words,  adenin  administered  combined  in 
nucleic  acid  loses  its  amino  (NH2)  group,  receives  three  atoms 
of  oxygen,  and  is  thereby  converted  into  uric  acid;  adenin  ad- 
ministered as  such  receives  two  atoms  of  oxygen,  but  does  not 
lose  its  NH2  group  at  the  point  for  the  attachment  of  the  third 
atom  of  oxygen.  This  work  attests  a  varying  behavior  of 
purin  bodies  in  accordance  with  their  method  of  chemical 
union  with  other  substances,  and  offers  a  suggestive  key  to 
certain  relations  observed  in  gout  (p.  546). 

When  theophyllin,  caffein,  and  theobromin,  the  methylated 
purins  found  in  tea,  coffee,  and  cocoa,  are  ingested  it  has  been 
stated  that  they  are  not  oxidized  to  uric  acid,  but  that  they 
increase  the  purin  bases  in  the  urine.2  However,  both  Levin- 
thai3  and  Stanley  Benedict4  have  found  the  uric  acid  elimina- 
tion to  increase  in  man  after  the  ingestion  of  1  to  1.5  gram  of 
caffein  daily. 

The  original  investigations  of  Horbaczewski  have  been 
considerably    extended    by    Schittenhelm    and    notably    by 

1  Minkowski:   "Archiv  fur  ex.  Path,  und  Pharm.,"  1898,  xli,  375. 

2  Kriiger  and  Schmid:  "Zeitschrift  fur  physiologische  Chemie,"  1901,  xxxii, 
104. 

3Levinthal:  Ibid.,  1912,  lxxvii,  259. 

4  Benedict,  S.  R.:   "The  Harvey  Lectures,"  1915-16. 


PURIN   METABOLISM — GOUT  533 

Walter  Jones,  especially  in  regard  to  their  explanation 
along  lines  of  enzymotic  activity. 

Jones  and  Partridge1  find  that  although  the  great  majority 
of  the  organs  of  the  body,  when  self-digested  at  400  (autolysis), 
convert  guanin  and  adenin  into  xanthin  and  hypoxanthin, 
presumably  through  the  action  of  enzymes,  extracts  of  the 
spleen  of  the  pig  cannot  convert  guanin  into  xanthin,  although 
they  can  convert  adenin  into  hypoxanthin.  Jones  therefore 
concludes  that  an  enzyme,  guanase,  which  normally  removes 
the  NH2  group  and  replaces  it  with  O,  is  wanting  in  the  pig's 
spleen,  while  adenase,  the  enzyme  acting  on  adenin  in  a  similar 
fashion,  is  present  there.     Such  a  reaction  would  read: 

CsHa^NHj     +     H20     =     C5H5HoO     +     XH3 

Adenin.  Hypoxanthin. 

Investigating  the  subject  further,  the  authors  found  that  the 
pancreas  contained  the  enzyme,  guanase,  which  converts 
guanin  into  xanthin. 

The  behavior  of  the  livers  of  different  animals  has  been 
investigated  by  Jones  and  Austrian.2  In  cattle  livers,  for  ex- 
ample, adenase,  guanase,  and  xanthin  oxidase  are  present, 
whereas  in  dog  livers  guanase  is  present,  adenase  occurs  in 
traces  only,  and  no  xanthin  oxidase  whatever  has  been  found. 
Hence  cattle  livers  may  form  uric  acid  from  adenin  and  guanin, 
while  dog  livers  only  convert  guanin  into  xanthin  and  the  other 
processes  are  arrested.  The  process  is  thus  graphically  repre- 
sented: 

Cattle  Livers.  Dog  Livers. 

Guanin.  Adenin.  Guanin.  Adenin. 


1°  i<  1°  I< 

Uric  Acid< Xanthin< Hypoxanthin.       Uric  Acid Xanthin Hypoxanthin. 

Xanthin  oxidase  present.  Xanthin  oxidase  and  adenase  absent. 

'Jones  and  Partridge:  "Zeitschrift  fur  physiol.  Chemie,"  1904,  xlii,  343; 
see  also  Levene,  "American  Journal  of  Physiology,"  1904,  xii,  276. 

2  Jones  and  Austrian:  "Zeitschrift  fur  physiologische  Chemie,"  1906,  xlviii, 
no. 


534  SCIENCE   OF   NUTRITION 

Furthermore  these  authors  find  that  the  guanase  is  absent 
from  pigs'  livers,  while  adenase  and  xanthin  oxidase  are  pres- 
ent. It  is  interesting  that  Mendel  and  Mitchell1  have  found 
in  the  liver  of  the  embryo  pig  at  an  early  age  the  same  specific 
enzymes  as  characterize  the  liver  of  the  adult  animal.  There 
was,  however,  a  considerable  delay  in  the  appearance  of  the 
enzyme  which  oxidizes  uric  acid  (see  below).  It  is  a  curious 
phenomenon  that  pigs  suffer  from  guanin  gout.  Their  normal 
urines  contain  not  only  uric  acid,2  but  also  large  amounts  of 
purin  bases.3    The  organs  of  the  pig  are  deficient  in  guanase.4 

Schittenhelm5  reports  that  human  livers  have  the  power  to 
form  uric  acid  from  added  purins,  and  he  believes  that  the 
power  to  oxidize  uric  acid  exists. 

Lauder  Brunton6  says  that  Stockvis,  of  Amsterdam,  in 
i860  found  that  crushed  tissue  had  the  power  to  destroy  uric 
acid.  This  question  has  recently  come  into  prominence  and 
it  has  been  shown  that  different  organs  have  different  powers 
in  this  regard,  and  that  the  same  organ  in  animals  of  different 
species  may  behave  quite  differently. 

Wiener7  showed  that  dog's  liver  and  pig's  liver  destroyed 
uric  acid,  whereas  calf's  liver  had  less  power  to  do  so,  or  none 
at  all.  The  kidney  pulp  of  various  animals  also  destroyed 
uric  acid. 

Schittenhelm8  finds  that  in  cattle  the  spleen,  lungs,  liver, 
intestine,  and  kidney  have  the  power  of  converting  purin  bases 
into  uric  acid  in  the  presence  of  a  constant  oxygen  supply. 
He  finds  a  complete  transformation  of  adenin,  as  follows: 
adenin,  hypoxanthin,  xanthin,  uric  acid.  Guanin  in  like  man- 
ner becomes  xanthin  and  this  again  is  converted  into  uric  acid. 

1  Mendel  and  Mitchell:   "American  Journal  of  Physiology,"  1907,  xx,  97. 

2  Schittenhelm  and  Bendix:  "Zeitschrift  fur  physiologische  Chemie,"  1906, 
xlviii,  140. 

3  Mendel  and  Lyman:    "Journal  of  Biological  Chemistry,"  1910,  viii,  115. 

4  Jones  and  Austrian:  "Zeitschrift  fur  physiologische  Chemie,"  1906,  xlviii, 
no. 

5  Kiinzel  and  Schittenhelm:   "Zentralblatt  fur  Stoffwechsel,"  1908,  iii,  721. 

6  Lauder  Brunton:   "Centralblatt  fur  Physiologie,"  1905,  xix,  5. 

7  Wiener:   "Archiv  fiir  exp.  Path,  und  Pharm.,"  1899,  xlii,  375. 

8  Schittenhelm:    "Zeitschrift  fiir  physiologische  Chemie,"  1905,  xlv,  145. 


PURIN   METABOLISM — GOUT  535 

He  finds  also  that  extracts  of  the  spleen,  intestines,  and  lungs 
have  no  power  to  destroy  uric  acid  as  formed  within  them,  but 
that  the  kidney,  muscle,  and  liver  extracts  possess  the  power 
to  destroy  the  new-formed  uric  acid. 

It  is  only  recently  that  evidence  has  accumulated  to  show 
that  the  long  believed  physiologic  oxidation  of  uric  acid  with 
the  production  of  urea  is  impossible.  To  understand  the  sub- 
ject it  is  necessary  to  consider  the  significance  of  allantoin 
which  was  first  discovered  by  Wohler  in  cows'  urine  in  1849. 
Salkowski1  reported  that  the  allantoin  excretion  increased  in 
dogs  after  the  administration  of  uric  acid.  The  transformation 
of  uric  acid  into  allantoin  takes  place  after  the  following  re- 
action : 

HN CO        +        H20        HN CO 


CO      C— NH  CO 

!     !!   Vo   —       I 


H2N 

">CO     +     C02 


HN C— NH       +       O        HN CH— NH 

Uric  acid.  Allantoin. 

Cohn2  gave  large  amounts  of  thymus  to  a  dog  and  found 
that  the  excretion  of  allantoin  was  greatly  increased,  though 
this  did  not  happen  in  man,  and  experiments  by  Minkowski,3 
performed  during  the  same  year,  showed  that  when  hypo- 
xanthin  was  fed  to  a  dog  77  per  cent,  of  it  appeared  in  the 
urine  as  allantoin,  while  4  per  cent,  was  eliminated  as  uric  acid. 
Mendel  and  White4  found  that  allantoin  was  eHminated  in  the 
urine  of  cats  and  dogs  after  the  intravenous  administration  of 
urates. 

It  was  long  believed  that  allantoin  was  an  intermediary 
product  of  the  oxidation  of  uric  acid.  It  is  due  to  Wiechowski 
that  the  subject  has  become  clarified.  Wiechowski5  found 
that  uric  acid  digested  with  the  pulp  of  dog's  liver  was  oxidized 
completely  to  allantoin  and  no  further,  and  also  that  uric 

1  Salkowski:   "Ber.  d.  d.  chem.  Ges.,"  1876,  ix,  719. 

2  Cohn:    "Zeitschrift  fiir  physiologische  Chemie,"  1898,  xxv,  507. 

3  Minkowski:    "Archiv  fiir  exp.  Path,  und  Pharm.,"  1898,  xli,  375. 

4  Mendel  and  White:    "American  Journal  of  Physiology,"  1904-5,  xii,  85. 

5  Wiechowski :   "Hofmeister's  Beitrage,"  1907,  ix,  295;  1908,  xi,  109. 


536  SCIENCE   OF   NUTRITION 

acid  injected  subcutaneously  into  a  dog  was  almost  completely 
eliminated  as  allantoin  in  the  urine.  These  results  were  de- 
pendent upon  the  accurate  method  for  the  determination  of 
allantoin  which  had  been  devised  by  the  experimenter.  It  is 
evident,  therefore,  that  the  oxidizing  enzyme  uricase,  which 
acts  upon  uric  acid,  carries  its  destructive  power  only  as  far  as 
the  production  of  allantoin,  which  is  the  end-product  of  purin 
oxidation. 

An  experiment1  made  many  years  ago  demonstrated  that 
if  an  Eck  fistula,  which  excludes  the  portal  blood  from  the 
liver,  be  created  in  a  dog,  uric  acid  appears  in  increased 
quantity  in  the  urine.  The  interpretation  long  placed  upon 
this  was  that  in  the  absence  of  the  liver  uric  acid  was 
not  oxidized.  Repeating  this  experiment,  Abderhalden, 
London,  and  Schittenhelm2  found  that  the  increase  in  uric 
acid  elimination  was  compensated  for  by  a  decrease  in  allan- 
toin excretion.  The  percentage  values,  contrasted  with  those 
in  normal  dogs'  urine  as  established  by  Wiechowski,  were  as 
follows : 

Eck  Fistula.  Normal. 

Allantoin 74-87  94~97 

Uric  acid 12-8  2-4 

Purin  bases 1-2  1-2 

It  is  evident  that  the  liver  is  not  the  only  organ  in  which 
uricase  converts  uric  acid  into  allantoin. 

Wiechowski  found  that  the  allantoin  excretion  of  the  cat 
followed  the  same  laws  as  obtain  in  the  dog,  and  Hunter  and 
Givens3  report  that  the  extent  and  behavior  of  the  allantoin 
excretion  of  the  Wyoming  coyote  is  practically  identical  with 
that  of  the  dog. 

Hunter  and  Givens4  state  that  the  excretion  of  purin 
bases  in  the  monkey  greatly  exceeds  the  elimination  of  uric 

1  Hahn,  Massen,  Nencki,  and  Pawlow:  "Archiv  flir  exp.  Path,  und  Pharm.," 
1893,  xxxii,  191. 

2  Abderhalden,  London,  and  Schittenhelm:  "Zeitschrift  flir  physiologische 
Chemie,"  1909,  lxi,  413. 

3  Hunter  and  Givens:  "Journal  of  Biological  Chemistry,"  1910-11,  viii,  449. 

4  Hunter  and  Givens:  Ibid.,  1914,  xvii,  37. 


PURIN   METABOLISM — GOUT  537 

acid,  a  condition  which  also  appears  in  the  horse,  sheep,  pig, 
and  goat.     For  the  monkey  the  percentage  figures  are: 

Per  Cent.  Purin  N. 

Uric  acid 7-8 

Allantoin 67 

Purin  bases 25-26 

When  allantoin  was  given  subcutaneously  to  the  monkey 
75  to  90  per  cent,  was  recovered  in  the  urine. 

Hunter  and  Givens1  present  the  following  table  showing 
the  relative  purin  content  in  the  urines  of  various  species  of 
animals : 


Order  and  Species. 


Per  Cent,  of  Purin — Allantoin  Nitrogen. 


Allantoin. 


Marsupialni : 

Oposum . . . 
Rodentia: 

Guinea-pig 

Rat 

Ungulata: 

Sheep 

Goat 

Cow 

Horse 

Pig 

Carnivora: 

Raccoon . . . 

Badger. . . . 

Dog 

Coyote. . . . 
Primates: 

Monkey. . . 

Man 


76.0 

oi. o 
93-7 

64.0 
81.0 
92. 1 
88.0 
92-3 

92.6 
96.9 

97.1 
95-6 

66.0 
2.0 


Uric  acid. 


Bases. 


19.0 

6.0 

6.0 

3-° 

3-7 

2.7 

16.0 

20.0 

7.0 

12.0 

7-3 

12.0 

1.8 

0.7 

°-5 

5-8 

54 
1.9 
1.9 
2.6 

2.0 
1.2 

i-3 

1.8 

8.0 

26.0 

90.0 

8.0 

An  extraordinary  exception  to  the  rule  of  oxidation  of 
uric  acid  to  allantoin  in  the  dog  was  discovered  by  Stanley 
Benedict2  to  be  characteristic  of  the  Dalmatian  hound,  or 
spotted  coach  dog.  The  urines  of  these  dogs  contain  large 
amounts  of  uric  acid.  When  uric  acid  is  administered  sub- 
cutaneously it  is  completely  eliminated  in  the  urine  instead  of 

1  Hunter  and  Givens:    "Journal  of  Biological  Chemistry,"  1914,  xviii,  403. 

2  Benedict,  S.  R.:   "The  Harvey  Lectures,"  1915-16. 


53^  SCIENCE   OF   NUTRITION 

being  oxidized  to  allantoin,  as  would  happen  ordinarily  in  the 
dog.     This  is  a  peculiar  racial  anomaly. 

The  urine  of  man  is  almost  free  from  allantoin  and  the 
10  to  15  milligrams  which  Wiechowski  found  therein  may  be 
accounted  for  as  originating  from  traces  of  the  substance  found 
in  common  foods.1 

Loewi2  showed  that  the  ingestion  of  the  same  amount  of 
nucleoprotein-containing  food  by  different  people  resulted  in 
the  excretion  of  the  same  increased  quantity  of  uric  acid  in  the 
urine,  and  he  surmised  that  the  uric  acid  which  was  produced 
in  the  human  being  was  not  oxidized.  Confirmation  of  this 
idea  was  given  by  the  discovery  of  Soetbeer  and  Ibrahim3 
that  the  subcutaneous  injection  of  uric  acid  in  man  led  to  its 
complete  elimination  in  the  urine. 

For  a  long  time  this  viewpoint  was  overshadowed  by  ex- 
periments which  showed  only  a  moderate  recovery  of  uric  acid 
in  the  urine  when  purin  bases  in  measured  quantities  were 
given  to  human  beings.  These  results,  which  were  interpreted 
to  be  due  to  the  oxidation  of  the  purins  through  the  uric  acid 
stage,  are  now  attributed  to  their  non-absorption  or  their 
putrefaction  in  the  intestinal  tract. 

Wiechowski4  found  that  allantoin  injected  subcutaneously 
is  completely  eliminated  in  human  urine,  which  is  normally  free 
from  it.  He  also  found  that  human  tissues  have  no  power  to 
oxidize  uric  acid;  it  can  always  be  completely  recovered. 
Therefore  the  human  organism  lacks  the  enzyme  uricase. 

In  concordance  with  these  results  Umber  and  RetzlafP 
find  that  if  uric  acid  be  dissolved  in  piperazin  and  be  injected 
into  a  healthy  human  being,  between  80  and  95  per  cent,  may 
be  recovered  in  the  urine;  also  Levinthal6  injected  1  gram  of 

1  Ackroyd:    "Biochemical  Journal,"  1911,  v,  400. 

2  Loewi:    "Archiv  fur  exp.  Path,  und  Pharm.,"  1900,  xliv,  1. 

3  Soetbeer  and  Ibrahim:  "Zeitschrift  fur  physiologische  Chemie,"  1902, 
xxxv,  1. 

4  Wiechowski:    "Archiv  fur  exp.  Path,  und  Pharm.,"  1909,  lx,  185. 

B  Umber  and  Retzlaff:  "Verhandlungen  des  271*11  Congresses  fur  innere 
Medizin,"  1910,  Sec.  Ill,  p.  436. 

*  Levinthal:    "Zeitschrift  fur  physiologische  Chemie,"  191 2,  lxxvii,  259. 


PURIN   METABOLISM — GOUT  539 

xanthin  dissolved  in  piperazin  into  the  vein  of  a  healthy 
human  subject,  and  concluded  that,  in  all  probability,  all  the 
xanthin  which  reached  the  metabolic  circulation  was  com- 
pletely eliminated  without  the  rupture  of  the  purin  nucleus,  the 
larger  part  being  oxidized  to  uric  acid  and  only  a  small  re- 
mainder passing  unchanged  through  the  organism. 

Finally,  the  experiments  of  Thannhauser  and  Bommes1 
deserve  attention.  When  adenosin  and  guanosin  were  admin- 
istered subcutaneously  to  normal  men,  between  75  and  82 
per  cent,  of  the  purin  bases  contained  in  them  were  eliminated 
in  the  urine  of  the  following  twenty-four  to  forty-eight  hours 
in  the  form  of  uric  acid.  These  water-soluble  purin-glucosids, 
adenosin  and  guanosin,  are  undoubtedly  intermediary  metabo- 
lites of  nucleic  acids. 

The  synthetic  origin  of  purins  in  metabolism  has  been 
recognized  since  the  work  of  Miescher  (see  p.  82).  Kossel2 
showed  that  purins  developed  in  the  incubated  egg,  which 
when  newly  laid  is  free  from  them  (see  also  p.  371). 

It  has  been  made  clear  that  in  mammals  the  purins  may  be 
derived  from  ingested  nucleoproteins,  but  this  cannot  be  the 
only  source,  since  purins  are  found  in  the  urine  during  star- 
vation and  on  a  diet  free  from  purins.  This  indicates  a  con- 
stant production  of  these  substances  in  metabolism.  Uric 
acid  and  purin  bases  from  this  source  have  been  termed  endog- 
enous by  Burian  and  Schur,  in  contradistinction  to  those  which 
are  eliminated  after  the  ingestion  of  nuclein-containing  food, 
which  are  called  exogenous. 

Burian  and  Schur3  also  established  the  fact  that  while  the 
endogenous  uric  acid  elimination  varied  between  0.3  and  0.6 
gram  daily,  according  to  the  individual,  it  did  not  vary  in 
the  same  individual,  but  was  a  constant  factor  in  his  metabo- 
lism. 

A  purin-free  diet  is  obtained  by  giving  such  articles  of  food 

1  Thannhauser  and  Bommes:  "Zeitschrift  fur  physiologische  Chemie,"  1014, 
xci,  336. 

2  Kossel:   Ibid.    1886,  x,  248. 

3  Burian  and  Schur:  "Pfluger's  Archiv,"  1901,  lxxxvii,  239. 


540  SCIENCE   OF   NUTRITION 

as  milk,  eggs,  bread,  potatoes,  fats,  and  sugars,  none  of  which 
contain  nuclear  material  which  forms  exogenous  purins  in  the 
body.  Burian  and  Schur  found  that  on  such  a  diet  the  uric 
acid  elimination  was  entirely  independent  of  the  quantity  of 
protein  ingested.  It  has  been  demonstrated  by  Rockwood1 
that  the  endogenous  uric  acid  elimination  is  independent  of  the 
calorific  value  of  the  diet.  Addition  of  500  calories  contained 
in  maple  sugar  to  a  diet  containing  2500  calories  did  not  affect 
the  excretion  of  uric  acid.  Rockwood's  experiments  extended 
over  a  long  period  of  time.  His  individuals  were  nourished  on 
milk,  eggs,  white  bread,  crackers,  cheese,  apples,  and  butter. 
The  constancy  of  the  uric  acid  output  in  the  same  individual  is 
seen  in  the  following  table — in  one  case  the  record  covering 
nearly  a  year: 

TABLE  SHOWING  THE  CONSTANCY  OF  THE  DAILY  ENDOG- 
ENOUS URIC  ACID  EXCRETION  IN  THE  SAME  INDIVIDUAL 
(TWO   SUBJECTS) 

Person  A.         Date,  1903.  Urine  N  in  Grams.         Uric  Acid,  Grams. 

January u-99  0.308 

February 11.58  0.305 

March 11.15  0.315 

May 12.63  0.321 

July 12.68  0.313 

November 9.99  0.298 

Person  B.      January 13.41  0.478 

March 13-92  0.452 

This  total  shows  the  constancy  of  the  output  of  endogenous 
uric  acid  in  the  same  individual  during  a  long  period.  Here 
the  difference  in  the  behavior  of  two  individuals  may  be 
ascribed  to  a  personal  idiosyncrasy  as  regards  the  capacity  of 
producing  uric  acid.  From  the  record  of  Chittenden's2  experi- 
ments, which  c6vered  a  period  of  twenty-one  months,  it  may 
be  observed  that  a  very  low  protein  diet  and  moderate  intake 
of  food  were  without  effect  on  the  output  of  uric  acid. 

The  source  of  the  endogenous  purins  has  been  the  cause  of 
considerable  speculation.     In  birds  there  is  a  large  synthetic 

1  Rockwood:    "American  Journal  of  Physiology,"  1904,  xii,  38. 

2  Chittenden:   "Physiological  Economy  in  Nutrition,"  1904,  p.  24. 


PURIN   METABOLISM — GOUT  54 1 

production  of  uric  acid  in  the  liver,  for  Minkowski1  has  shown 
that  extirpation  of  the  liver  in  geese  leads  to  a  replacement  of 
uric  acid  by  ammonia  and  lactic  acid  in  the  urine.  The 
following  analyses2  give  an  idea  of  the  composition  of  the  urine 
of  birds: 

Duck's  Urine.  Fowl's  Urine. 

(Total  N  =  0.615  gm.)    (Total  N  =  0.759  gm.) 
*  Per  Cent.  Per  Cent. 

Ammonia 3.20  1.49 

Urea 4.19  0.99 

Uric  acid 77.88  85.86 

Purins 0.53  1.69 

Colloidal  N 4.09 

Amino-acid 2.71  2.52 

Unknown 7.40  7.45 

100.00  100.00 

The  method  of  the  synthetic  production  of  purins  is  en- 
tirely conjectural. 

Ingestion  of  pyrimidin  bases  (p.  528)  has  failed  to  yield 
purins  in  the  organism.3 

Burian4  has  investigated  the  source  of  the  endogenous  pu- 
rins and  comes  to  the  conclusion  that  only  a  small  part  of 
the  endogenous  uric  acid  arises  from  the  nucleoproteins  of 
cellular  tissue  or  those  of  dead  leukocytes.  It  would  require 
too  large  a  destruction  of  tissue  to  provide  from  0.3  to  0.6  gram 
uric  acid  or  0.1  to  0.2  gram  purin  nitrogen  daily  in  the  urine  if 
it  all  arose  from  cell  nuclein. 

Burian  and  Schur's5  analyses,  showing  the  content  of  purin 
nitrogen  in  various  tissues,  are  given  below: 

TABLE  SHOWING  THE  QUANTITY  OF  PURIN  N  CONTAINED  IN 
100  GRAMS   OF  DIFFERENT  ANIMAL  TISSUES 

Total  Purin  N.  N  in  Free  Purin  Bases. 

Meat 0.06  0.045 

Thymus 0.45  0.05 

Calf's  liver 0.12  0.033 

Calf's  spleen 0.16  0.046 

1  Minkowski  and  Naunyn:  "Archiv  ftir  experimentelle  Path,  und  Pharm.," 
1886.  xxi,  41. 

2  Szalagyi  and  Kriwuscha:    "Biochemische  Zeitschrift,"  1914,  lxvi,  126. 

3  Steudel:    "Zeitschrift  fur  physiologische  Chemie,"  1903,  xxxix,  136. 

4  Burian:  Ibid.,  1905,  xliii,  532. 

5  Burian  and  Schur:   "Pfliiger's  Archiv,"  1900,  lxxx,  308. 


542  SCIENCE   OF    NUTRITION 

To  obtain  the  amount  of  endogenous  uric  acid  present  in 
the  urine,  if  it  were  produced  by  the  destruction  of  nucleo- 
proteins,  it  would  be  necessary  to  destroy  completely  a  quan- 
tity of  nucleoprotein  equal  to  that  contained  in  more  than 
ioo  grams  of  liver.  It  does  not  seem  possible  that  nuclein  de- 
struction or  nuclein  metabolism  could  reach  this  extent. 

Burian  concludes  that  in  the  resting  muscle  there  is  a  con- 
stant production  of  hypoxanthin  which  is  converted  into  uric 
acid  through  the  activity  of  the  xanthin  oxidase.  In  the  active 
muscle  there  is  a  greater  production  of  hypoxanthin  which  is 
not  completely  oxidized  on  account  of  a  local  oxygen  de- 
ficiency. 

It  had  been  found  by  many  previous  observers  that  exercise 
has  no  effect  on  the  purin  excretion  in  the  urine  of  twenty-four 
hours  in  man.  Burian,  however,  finds  a  large  increase  in  the 
purin  elimination  for  an  hour  or  two  after  severe  muscular 
exercise,  and  this  is  followed  by  a  compensatory  reduction  in 
the  output  during  those  subsequent  hours  which  represent  the 
interval  of  weariness  in  the  muscle. 

These  observations  were  confirmed  by  the  work  of  Rock- 
wood,1  who  saw  that  the  purin  excretion  was  less  during  the 
night  than  during  the  day,  and  by  the  work  of  Pfeil,2  who  found 
a  constant  morning  rise  in  the  output  of  purins  in  human 
urine. 

These  facts  confirm  Burian's  contention  that  the  most  gen- 
eral source  of  endogenous  purins  is  a  constant  production 
of  hypoxanthin  in  muscle,  a  production  which  varies  with  the 
individual  and  is  possibly  proportional  to  the  mass  of  his  mus- 
culature. Comparable  to  this  is  the  constant  production  of 
creatinin  (p.  209).  Such  of  the  purin  bases  as  escape  oxida- 
tion may  be  excreted  by  the  blood  flowing  through  the  kidney 
even  as  uric  acid  is  excreted  under  the  same  circumstances. 

Siven3  does  not  believe  that  muscular  work  appreciably 
raises  the  production  of  endogenous  purins.     He  thinks  that 

1Rockwood:    Loc.cit. 

2  Pfeil:    "Zeitschrift  fur  physiologische  Chemie,"  1904,  xl,  1. 

3  Siven:   Abstract  in  "Zentralblatt  fur  Stoffwechsel,"  1906,  i,  81. 


PURIN   METABOLISM — GOUT  543 

the  reduction  in  purin  elimination  during  the  night  time  is  due 
to  general  inactivity  of  all  the  tissues,  and  shows  that  when  an 
evening  meal  containing  much  protein  is  taken  and  the  kidney 
is  made  thereby  to  functionate  during  the  night,  then  the  purin 
elimination  is  increased.  Burian's  discovery  of  increased 
elimination  during  work  was  perhaps  due  to  the  fact  that  the 
work  was  accomplished  during  the  morning  hours,  when  an  in- 
creased elimination  due  to  purins  retained  during  the  night 
would  normally  occur. 

Mendel  and  Brown1  have  determined  the  hourly  excretion 
of  uric  acid  as  influenced  by  the  ingestion  of  meat,  liver,  and 
other  animal  tissues.  The  increase  in  the  eliminated  uric  acid 
is  very  marked  and  reaches  a  maximum  two  or  three  hours 
after  the  ingestion  of  these  animal  tissues.  Thus  after  the 
ingestion  of  600  grams  of  chopped  meat  the  uric  acid  elimina- 
tion, which  had  been  19  milligrams,  rose  during  the  following 
three  hourly  periods  to  28,  88,  and  98  milligrams,  and  then 
fell  in  successive  hours  to  79,  73,  51,  36,  25,  and  22  milligrams. 
It  will  be  seen  later  that  such  curves  of  exogenous  uric  acid 
excretion  do  not  occur  in  the  gouty  patient  in  whom  there  is 
uric  acid  retention  (see  p.  548). 

The  recent  studies  of  Stanley  Benedict2  concerning  the 
uric-acid  content  of  the  blood  have  brought  to  light  some  new 
and  important  facts.  Fowl's  blood  had  heretofore  been  ac- 
counted much  richer  in  uric  acid  than  ox  blood.  Benedict 
finds  this  to  be  true  only  of  the  blood-serum,  which  in  the  fowl 
contains  uric  acid  which  circulates  uncombined,  whereas  the 
blood-serum  of  the  ox  is  almost  entirely  free  from  uric  acid. 
Considered  as  a  whole,  however,  ox  blood  yields  0.50  milli- 
gram of  uncombined  uric  acid  in  100  c.c.  of  blood.  This  is 
the  amount  which  had  been  previously  reported,  but  after 
hydrolysis  6.7  milligrams  of  uric  acid  were  isolated  and  identi- 
fied. This  is  entirely  contained  in  the  corpuscles  and  amounts 
to  50  per  cent,  more  than  the  uric  acid  content  of  chickens' 

1  Mendel  and  Brown:  "Journal  of  the  American  Medical  Association," 
1907,  xlix,  896. 

2  Benedict,  S.  R.:    "Journal  of  Biological  Chemistry,"  1915,  xx,  633. 


544  SCIENCE   OF   NUTRITION 

blood.     These  results  throw  additional  light  upon  Minkowski's 
conception  of  the  nature  of  gout,  soon  to  be  considered. 


The  subject  of  gout  is  one  of  the  most  baffling  in  the  liter- 
ature of  metabolism.  Despite  the  brilliant  work  upon  the 
purins  during  the  last  ten  years,  work  which  has  been  illumi- 
nated by  the  discovery  of  the  formula  of  nucleic  acid  by 
Levene,  the  nature  of  gout  remains  as  much  of  a  mystery  as 
ever. 

Just  as  the  whole  trouble  in  diabetes  turns  upon  the  in- 
ability of  the  organism  to  destroy  sugar,  so  the  symptoms 
manifested  in  gout  are  dependent  upon  the  deposit  of  acid 
urate  of  sodium  in  certain  localities.  One  of  the  earliest  de- 
scriptions of  gout  comes  from  Sydenham,  who  suffered  for 
forty  years  from  the  disease  and  published  an  extended  account 
of  it  in  1683.  It  was  Garrod1  who  first  established  the  fact 
that  uric  acid  was  present  in  the  blood  of  gouty  persons.  He 
believed  that  this  excess  of  urate  was  the  cause  of  gout,  the 
excess  being  deposited  from  the  blood  in  the  joints  in  the  form 
of  crystals.  The  problem  of  metabolism  in  gout  is  a  problem 
of  the  factors  entering  into  the  cause  of  this  deposit  of  urate. 
The  general  metabolism,  exclusive  of  the  purin  factor,  is  ex- 
actly the  same  as  in  health.  Magnus-Levy2  proved  that  the 
oxygen  absorption  and  carbon  dioxid  elimination  is  the  same 
in  gout  as  in  health.  The  cause  of  the  trouble  must  be  sought 
elsewhere  than  in  a  reduced  general  oxidation  power  of  the 
tissues. 

Clinical  experience  teaches  that  the  predisposing  causes  are 
excessive  eating,  little  muscular  exercise,  the  abuse  of  alcoholic 
beverages,  and  lead-poisoning. 

Beebe3  has  administered  alcohol  in  various  forms  to  a 
normal  individual.     He  finds  that  even  large  doses  have  no 

1  Garrod:    "The  Nature  and  Treatment  of  Gout,"  1859. 

2  Magnus-Levy:   "Berliner  klinische  Wochenschrift,"  1896,   xxxiii,  416. 

3  Beebe:   "American  Journal  of  Physiology,"  1904,  xii,  13. 


PURIN   METABOLISM — GOUT  545 

effect  on  the  hourly  excretion  of  uric  acid  in  a  fasting  man. 
The  endogenous  purin  metabolism  is  therefore  unchanged  by 
the  ingestion  of  alcohol.  It  is  important  to  know  that  alcohol 
is  apparently  without  effect  upon  such  part  of  the  purins  as 
may  be  directly  derived  from  cell  metabolism.  Further  in- 
vestigation of  this  subject  by  Landau1  has  revealed  the  fact 
that  the  influence  of  alcohol  is  different  in  different  individuals, 
and  that  usually  there  is  a  slight  increase  in  the  output  of  en- 
dogenous purins  after  taking  alcohol.  Mendel  and  Hilditch2 
report  the  same  results.  Administration  of  alcohol  equal  to 
500  calories,  together  with  a  purin-free  diet,  to  a  man  pre- 
viously unaccustomed  to  alcohol  caused  a  slight  decrease  in  the 
elimination  of  nitrogen  and  a  slight  increase  in  that  of  uric  acid. 
Otherwise  the  urinary  analysis  showed  little  or  no  change, 
even  when  alcohol  was  administered  for  weeks. 

Pollak3  has  shown  that  in  chronic  alcoholics  the  retention 
of  ingested  purins  is  favored. 

Minkowski,4  with  a  master  hand,  summarized  modern 
knowledge  concerning  gout  as  follows: 

1.  The  deposit  of  urate  in  the  tissues  is  the  first  change 
which  takes  place  in  the  formation  of  the  specific  gouty  nodules. 
These  tissues  are  not  necrotic,  as  taught  by  Ebstein. 

2.  The  tissue  changes  in  the  vicinity  of  the  gouty  nodules 
are  in  part  due  to  mechanical,  in  part  to  chemical  or  osmotic, 
action,  caused  by  the  precipitated  urates. 

3.  The  acute  inflammation  in  gout,  as  observed  during  the 
attack,  is  produced  in  the  vicinity  of  the  urate  deposits  through 
some  unknown  cause.  Traumatic,  toxic,  or  infectious  ele- 
ments appear  to  be  collectively  active  in  this  regard.  The 
attack  probably  constitutes  the  reaction  of  the  organism 
to  rid  itself  of  uric  acid,  an  effect  which  is  only  partly 
realized. 

1  Landau:   "Deutsches  Archiv  fur  klinische  Medizin,"  1909,  xcv,  280. 

2  Mendel  and  Hilditch:  "American  Journal  of  Physiology,"  1910-11,  xxvii, 
1. 

3  Pollak:   "Deutsches  Archiv  fur  klin.  Med.,"  1906,  lxxxviii,  224. 

4  Minkowski:  von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1904, 
ii,  p.  277. 

35 


546  SCIENCE   OF   NUTRITION 

4.  An  accumulation  of  uric  acid  in  the  blood  is  a  constant 
accompaniment  of  gout. 

5.  The  increased  quantity  of  uric  acid  in  the  blood  must  not 
be  considered  as  the  cause  of  the  precipitation  of  urates  in  the 
gouty  nodules.  There  must  be  certain  local  influences  which 
favor  the  deposit  of  urates;  for  Klemperer  has  shown  that  the 
blood  of  gouty  patients  may  dissolve  much  more  uric  acid  than 
is  actually  present  in  it;  and  again,  the  blood  in  leukemia  may 
contain  as  much  uric  acid  as  in  gout,  without  there  being  any 
indication  of  a  deposit  of  urate. 

6.  The  uric  acid  elimination  is  the  same  in  the  gouty  as  in 
the  normal  person,  except  at  the  time  of  the  attack.  Before 
the  attack  there  is  retention,  but  during  and  after  the  attack 
an  increased  excretion  of  uric  acid  in  the  urine. 

7.  The  accumulation  of  uric  acid  in  the  blood  is  not  due  to 
a  diminished  oxidation  of  uric  acid,  but  rather  to  a  diminution 
in  the  quantity  excreted  in  the  urine. 

8.  It  is  not  certain  that  the  lessened  excretion  of  uric  acid 
is  due  to  a  disturbance  of  renal  function.  Very  likely  it  de- 
pends upon  the  presence  of  uric  acid  in  some  abnormal  chem- 
ical union.  This  abnormal  substance  may  be  with  difficulty 
eliminated  in  the  urine,  but  may  lend  itself  readily  to  the 
formation  of  tophi  (p.  532). 

9.  The  ultimate  cause  of  the  unusual  behavior  of  uric  acid 
in  gout  is  probably  an  abnormal  metabolism  within  the  nuclei 
of  the  cells,  where  the  nucleic  acid  content  is  the  means  of  solu- 
tion and  conveyance  not  only  of  the  purin  bases  but  also  of 
uric  acid. 

The  opinions  of  other  modern  workers  vary  somewhat  from 
those  of  Minkowski,  as  appears  in  the  following: 

Almagia,1  in  Hofmeister's  laboratory,  has  performed  some 
interesting  experiments  and  concludes  that  the  older  view  of 
Garrod  is  correct — that  is,  that  an  excess  of  urates  in  the  blood 
is  the  cause  of  gout.  Almagia  finds  that  thin  strips  of  cartilage 
suspended  in  dilute  neutral  solutions  of  sodium  urate  absorb 

1  Almagia:    "Hofmeister's  Beitrage,"  1906,  vii,  466. 


PURIN  METABOLISM — GOUT  547 

the  salt,  do  not  destroy  it,  but  cause  it  to  be  deposited  in  fine 
crystals  within  the  cartilage.  He  furthermore  injected  5  to 
7  grams  of  uric  acid  into  the  peritoneal  cavity  of  rabbits, 
a  dose  which  usually  killed  them.  On  testing  the  liver,  spleen, 
muscles,  and  lungs  with  the  murexid  test  for  uric  acid,  negative 
results  were  obtained,  whereas  cartilage  gave  a  positive  reac- 
tion indicating  the  presence  of  urates.  Almagia  concludes  that 
the  deposit  of  urates  in  the  cartilage  of  a  gouty  patient  is  but 
the  result  of  a  temporary  or  permanent  increase  in  the  uric  acid 
content  of  the  blood.  The  liability  of  cartilage  to  contain 
deposits  of  urates  has  received  no  satisfactory  explanation. 
Exposure  to  cold,  stagnation  of  the  blood  flow,  and  the  rich- 
ness of  cartilage  in  sodium  salts  have  been  suggested  as  pos- 
sible reasons  for  the  precipitation  of  the  urates. 

In  leukemia,  where  there  must  be  a  large  destruction 
of  nucleoprotein,  as  evidenced  by  a  report  concerning  a  patient 
who  eliminated  12  grams  of  uric  acid  during  the  last  forty  hours 
of  life,  there  is  no  gout.1  Folin  reports  that  normal  human 
blood  contains  about  1.5  to  2.5  milligrams  of  uric  acid  per 
100  c.c.  and  that  this  quantity  is  exceeded  not  only  in  gout  but 
also  in  leukemia,  lead-poisoning,  and  in  nephritis.  Folin 
and  Denis2  state  that  in  true  gout  there  is  no  increase  in  the 
quantity  of  non-protein  nitrogen  in  the  blood,  though  this 
increase  appears  in  arthritis  deformans.  They  recommend 
this  as  a  means  of  differential  diagnosis  between  gout  and 
arthritis. 

Magnus-Levy,3  Vogt,4  and  Reach5  were  the  first  to  discover 
that  the  administration  of  glands  rich  in  nucleoprotein,  such 
as  thymus  and  pancreas,  to  gouty  persons  did  not  cause  as 
large  an  excretion  of  uric  acid  in  the  urine  as  when  the  same 
amounts  of  these  materials  were  given  to  normal  individuals. 

The  work  of  Soetbeer6  is  of  the  best  modern  character,  and 

1  Magnus-Levy:    "Virchow's  Archiv,"  1898,  clii,  107. 

2  Folin  and  Denis:   "Archives  of  Internal  Medicine,"  1915,  xvi,  33. 

3  Magnus-Levy:    "Zeitschr.  fur  klin.  Med.,"  1899,  xxxvi,  414. 

4  Vogt:   "Deutsches  Arch,  fur  klin.  Med.,"  1901,  lxxi,  21. 

6  Reach:   "Miinchener  med.  Wochenschr.,"  1902,  xlix,  1215. 

6  Soetbeer:   "Zeitschrift  fiir  physiologische  Chemie,"  1904,  xl,  54. 


548  SCIENCE   OF   NUTRITION 

illustrates  the  retention  of  uric  acid  in  gout.  Soetbeer 
compared  the  excretion  of  uric  acid  by  gouty  people  during 
three-hour  intervals  with  that  of  normal  individuals,  as  ob- 
served by  Pfeil  (p.  542).  In  one  case  of  long-standing  gout, 
of  light  character  and  with  long  intervals  between  the  attacks, 
there  was  little  variation  from  the  normal  in  the  uric  acid  ex- 
cretion. In  another  case  of  gout,  a  patient  who  was  examined 
between  the  attacks  showed  no  increase  in  uric  acid  output 
after  changing  from  a  purin-free  diet  to  one  containing  320 
grams  of  meat,  and  showed  only  a  slight  increase  in  elimination 
after  640  grams  of  meat  were  given.  These  results  were  ob- 
tained six  weeks  after  the  last  attack  and  at  a  time  when  the 
patient  was  entirely  free  from  pain.  In  still  another  case  350 
grams  of  meat  were  given  during  the  attack  to  a  gouty  patient 
who  had  no  fever  and  whose  urine  was  free  from  albumin  and 
sugar.     The  results  were  as  follows: 

Uric  Acid 
in  Grams. 

Diet  free  from  purins 0.276 

."      "       "         "      0.328 

Diet  +  350  grams  meat 0.316 

"  "        "         "     0.270 

"     Q-255 

In  this  experiment  even  during  the  days  of  purin-free  diet 
there  was  no  "morning  rise"  noted  as  a  normal  incident  by 
Pfeil.  The  hourly  uric  acid  excretion  was  very  even.  The 
kidney  was  apparently  removing  uric  acid  up  to  the  limit  of  its 
capacity. 

Hefter1  administered  uric  acid  subcutaneously  to  a  gouty 
patient  and  recovered  only  n  per  cent,  of  it  in  the  urine  in 
contrast  with  a  recovery  of  86  per  cent,  in  the  normal  indi- 
vidual. Thannhauser  and  Bommes2  report  that  although 
between  75  and  82  per  cent,  of  the  purin  content  of  1  gram  of 
adenosin  when  subcutaneously  administered  to  normal  men 
appears  as  uric  acid  in  the  urine,  and  the  uric  acid  content  of 

1  Hefter:    "Deutsches  Archiv  fur  klin.  Med.,"  1913,  cix,  322. 

2  Thannhauser  and  Bommes:  "Zeitschrift  fur  physiologische  Chemie,"  1914, 
xci,  336. 


PURIN   METABOLISM — GOUT  549 

the  blood  does  not  rise,  yet  in  severe  gout  this  procedure  is  not 
followed  by  additional  excretion  of  uric  acid,  though  uric  acid 
does  increase  in  the  blood.  Three  of  four  gouty  patients  had 
attacks  of  gout  after  this  treatment.  The  authors  state  that 
the  conclusion  is  unavoidable,  that  gout  is  due  to  a  disturbance 
in  the  elimination  of  uric  acid. 

Denis1  finds  that  there  is  no  increase  in  the  uric  acid  con- 
tent of  the  blood  of  man  after  the  ingestion  of  foods  rich  in 
purins,  except  in  cases  of  renal  insufficiency. 

The  drugs  which  are  used  in  rheumatism,  arthritis,  and 
gout,  such  as  salicylate  of  soda,  aspirin,  and  atophan,  cause  an 
increased  elimination  of  uric  acid  in  the  urine  and  a  concomi- 
tant fall  in  the  quantity  of  uric  acid  present  in  the  blood.2 
Salicylate  of  sodium  when  given  in  amounts  to  produce  no  sal- 
icylate intoxication  (such  as  ringing  in  the  ears)  has  no  effect 
upon  the  basal  metabolism  of  normal  men,  though  the  uric 
acid  and  total  nitrogen  elimination  is  somewhat  increased.3 

The  discovery  of  Stanley  Benedict  of  the  large  amount  of 
uric  acid  combined  in  the  corpuscles  of  ox  blood  lends  added 
significance  to  the  idea  of  Minkowski  that  the  deposition  of 
urates  in  gout  may  be  dependent  upon  some  abnormal  chemical 
union  of  the  uric  acid  which  breaks  up,  yielding  urates  for  the 
construction  of  tophi.  The  possible  importance  of  this  factor 
should  not  be  lost  sight  of.4 

Miller  and  Jones5  were  unable  to  find  any  variation  from 
the  normal  in  the  distribution  of  the  purin  enzymes  in  the 
tissues  of  a  gouty  individual. 

Linser6  tells  how  a  gouty  individual  suffering  from  eczema 
was  treated  with  the  Rontgen  rays.  Although  the  person  was 
on  a  purin-free  diet,  the  treatment  invariably  brought  on  an 

1  Denis:    "Journal  of  Biological  Chemistry,"  1915,  xxiii,  147. 

2  Jackson  and  Blackfan:  "Albany  Medical  Annals,"  1907,  xviii,  24;  Rock- 
wood:  "American  Journal  of  Physiology,"  1909-10,  xxv,  34;  Fine  and  Chace: 
"Journal  of  Biological  Chemistry,"  1915,  xxi,  371;  Denis:  "Journal  of  Pharm. 
and  ex.  Ther.,"  1915,  vii,  601. 

3  Denis  and  Means:   "Journal  of  Pharm.  and  ex.  Ther.,"  1916,  viii,  273. 

1  Minkowski:    "Zeitschrift  fur  physiologische  Chemie,"  1913,  lxxxviii,  159. 

6  Miller  and  Jones:  Ibid.,  1909,  lxi,  395. 

6  Linser:   "Therapie  der  Gegenwart,"  1908,  No.  4. 


550  SCIENCE   OF   NUTRITION 

attack  of  gout  on  account  of  the  increased  production  of  uric 
acid  within  the  body  which  normally  follows  such  treatment. 

Gudzent1  states  that  monosodium  urate  occurs  in  the  blood 
in  two  isomeric  forms,  the  more  soluble  lactam  form  being 
readily  convertible  into  the  less  soluble  and  more  stable  lactim 
form,  these  having  been  chemically  differentiated  by  Emil 
Fischer.  While  ioo  c.c.  of  blood  dissolve  18.4  milligrams  of 
the  first  salt,  they  dissolve  only  8.4  milligrams  of  the  second. 
Gudzent2  maintains  that  the  inhalation  of  radioactive  emana- 
tions leads  to  an  increased  elimination  of  uric  acid  in  the 
gouty,  due  to  the  conversion  of  the  lactim  form  of  uric  acid  into 
the  lactam  form.  However,  Wiechowski3  denies  the  influ- 
ence of  radium  upon  the  solubility  of  uric  acid,  though  he  finds 
that  the  emanations  bring  about  a  rise  in  the  elimination  of 
uric  acid  not  only  in  gouty  persons  but  also  in  normal  indi- 
viduals. He  believes  with  His  that  trie  emanations  may  re- 
duce the  inflammatory  processes  in  gout,  thereby  indirectly 
favoring  more  normal  conditions  and  leading  to  the  elimination 
of  uric  acid.  There  is  little  or  no  influence  exerted  by  radium 
emanations  upon  the  respiratory  metabolism,4  although  it  is 
stated  that  the  ingestion  of  one  hundred  times  the  usual  thera- 
peutic dose  has  caused  an  increase  in  metabolism  of  17  per 
cent.5 

Von  Noorden  and  Schliep6  suggest  that  gouty  patients  be 
tested  for  their  "tolerance"  for  purin  bodies  just  as  diabetics 
are  tested  for  their  tolerance  for  carbohydrates;  400  grams 
of  meat  contain  0.24  gram  of  purin  nitrogen,  which  is  the 
equivalent  of  0.72  gram  uric  acid.  A  patient  was  put  on  a 
purin-diet  free;  was  given  400  grams  of  meat,  then  put  on  a 

1  Gudzent:    "Zeitschrift  fur  physiologische  Chemie,"  1909,  lxiii,  455. 

2  Gudzent:    "Zeitschrift  fur  klin.  Med.,"  1910,  lxxi,  304;  1913,  lxxviii,  266. 

3  Knaffl-Lenz  and  Wiechowski:  "Zeitschrift  fur  physiologische  Chemie," 
191 2,  lxxvii,  303. 

4  Silbergleit :  "Berliner  klinische  Wochenschrift,"  1908,  xlv,  13;  1909,  xlvi, 
1205. 

5  von  Benczur  and  Fuchs:  "Zeitschrift  fiir  ex.  Path,  und  Ther.,"  1912-13, 
xii,  564. 

6  von  Noorden  and  Schliep:  "Berliner  klinische  Wochenschrift,"  1905, 
xlii,  1297. 


PURIN   METABOLISM — GOUT  55 1 

purin-free  diet  again,  and  afterward  was  tested  with  200  grams 
of  meat.     The  results  were  as  follows: 

Uric  Acid 
Day.  Diet.  in  Grams. 

4 Purin  free 0.462 

5 "  "    +  400  gm.  meat 0.522 

6 "  "     +  400  gm.  meat 0.544 

7 "  "     °-539 

8 "  "     0.528 

9 "  "     0458 

10 "  "    +  200  gm.  meat 0.549 

11 "  "     +  200  gm.  meat 0-655 

12 \     0.647 

13 °-499 

14 "  "     °-433 

The  authors  conclude  that  while  the  increased  uric  acid 
output  after  giving  400  grams  of  meat  is  not  what  it  would  be 
normally,  yet  after  giving  200  grams  the  quantity  of  additional 
uric  acid  is  fully  eliminated.  Hence  this  patient  had  a  toler- 
ance for  the  purins  in  200  grams  of  meat. 

Dietetic  rules  for  gouty  sufferers  are  intended  to  combat 
the  fundamental  anomalies  of  the  metabolism.  The  organism 
must  not  be  overloaded  with  uric  acid.  Minkowski's  rules1 
for  treatment  of  gout  may  be  thus  abstracted:  Sweetbreads, 
liver,  and  kidney  are  to  be  strictly  excluded  from  the  diet  since 
they  contain  purin  bases  in  large  quantity.  Meat  is  to  be 
taken  in  moderation  only.  Wine  should  be  taken  sparingly 
or  not  at  all,  and  beer  rigidly  excluded  on  account  of  the  nuclein 
in  yeast.  Cathartics  may  be  given  to  rid  the  intestine  of  purin 
bodies  excreted  into  the  intestinal  canal,  and  water-drinking, 
which  promotes  a  larger  flow  of  urine  and  increased  uric  acid 
elimination,  is  strongly  to  be  commended.  The  diet  for  a 
gouty  patient  should  contain  each  day  100  or  120  grams  of 
protein,  80  or  100  grams  of  fat,  and  250  or  300  grams  of  car- 
bohydrates (2200  to  2600  calories).  This  should  not  include 
more  than  from  200  to  250  grams  of  meat  per  day.  Indigest- 
ible cakes,  pies,  rich  foods,  and  heavy  salads  should  be  forbid- 
den. Moderation  and  self-control  are  the  watchwords  for 
the  gouty  sufferer. 

1  Minkowski:    "Deutsche  medizinische  Wochenschrift,"  1905,  xxxi,  409. 


552  SCIENCE   OF   NUTRITION 

It  is  impossible  to  oxidize  uric  acid,  and  no  treatment  now 
known  increases  its  solubility.  Minkowski  hopes  that  some 
organic  compound  may  be  discovered  which  will  accomplish 
this  purpose. 

Bearing  the  facts  of  the  above  discussion  in  mind,  the 
reader  will  comprehend  that  present-day  doctrines  concerning 
metabolism  in  gout  may  shortly  become  entirely  obsolete 
through  new  and  far-reaching  discoveries. 


CHAPTER  XX 

THE  INFLUENCE  OF  CERTAIN  DRUGS   UPON 
METABOLISM 

Important  work  concerning  the  influence  of  certain  drugs 
upon  the  basal  metabolism  in  normal  men  has  been  carried  out 
by  Higgins  and  Means1  in  EdsalPs  clinic  at  Boston.  They 
present  a  summary  of  their  findings  in  the  following  table: 

THE  INFLUENCE   OF   DRUGS   ON  METABOLISM 


Aver- 
age 
Dose. 

Action. 

Drug. 

Respiratory 
Center. 

Bronchial 
Musculature. 

Metabolism. 

Increase. 
Increase. 

Generally 
slightly 
increased. 

None. 

Either 
slight  de- 
crease or 
none. 

None. 

Respiration 
Rate. 

Pulse-rate. 

Atropin 

i.o  mg. 
0.4  gm. 
0.1  gm. 

4-5  mg- 
16.0  mg. 

S-O  mg. 

None. 

Stimulation. 

None. 

None. 

Either  depres- 
sion or  none. 

Depression. 

Dilation. 

Either  dila- 
tion or  none. 

Either  dila- 
tion or  none. 

Probably 

none. 
Constriction.* 

Constriction. 

None. 

Increase. 

None. 

None. 

Slight  in- 
crease, t 

None. 

Fall,  then 
rise. 

Camphor 

None. 

None. 

None  or 
decrease. 

Slight  de- 

crease. 

*  Or  none,  when  the  bronchi  are  already  constricted. 

t  This  obviously  does  not  apply  to  large  doses  of  morphin. 


They  report  that  caffein  caused  a  rise  in  the  metabolism 
equal  to  15  per  cent,  without  changing  the  pulse-rate.  The  in- 
crease after  camphor  was  8  per  cent,  and  after  atropin  only  4 
per  cent,  above  the  normal  basal  metabolism.  That  thera- 
peutic doses  of  strychnin  cause  no  increase  in  metabolism  is 
significant. 

1  Higgins  and  Means:  "Journal  of  Pharmacology  and  Experimental  Thera- 
peutics," 1915,  vii,  1. 

553 


554  SCIENCE    OF    NUTRITION 

Unpublished  results  of  Means,  Aub,  and  DuBois  show  that 
large  doses  of  caffein  given  to  normal  individuals  cause  an  in- 
crease in  the  basal  metabolism  of  10  to  30  per  cent,  without  in- 
creasing the  pulse-rate  or  the  body  temperature. 

Other  unpublished  data  from  the  Russell  Sage  Institute  of 
Pathology,  and  taken  from  investigations  by  Eggleston  and 
DuBois,  show  that  no  change  in  metabolism  occurs  in  cardiac 
cases  after  the  administration  of  full  therapeutic  doses  of  digi- 
talis which  markedly  reduce  the  heart  rate. 

The  influence  of  large  doses  of  caffein  appears  at  first 
thought  to  be  remarkable,  the  basal  heat  production  rising  to 
the  level  found  after  the  ingestion  of  large  quantities  of  meat. 
The  increase  is  slight,  however,  when  compared  with  the  stim- 
ulation of  metabolism  by  muscular  exercise.  It  appears  great 
only  when  compared  with  the  immutability  of  the  level  of  the 
normal  basal  metabolism,  a  state  in  which  the  heat  production 
is  subservient  to  the  requirement  of  energy  on  the  part  of  the 
cells  for  the  maintenance  of  life,  the  requirement  being  so 
regulated  and  adjusted  that  the  heat  loss  per  square  meter  of 
surface  is  approximately  40  calories  per  hour,  while  the  body 
temperature  is  maintained  at  a  constant  level. 


CHAPTER   XXI 

FOOD  ECONOMICS1 

The  consideration  of  the  food  supply  from  a  national 
standpoint  was  forced  upon  Germany  at  the  outbreak  of  the 
great  war  which  is  now  in  progress.  Eminent  scientists  com- 
bined in  a  report  upon  the  prospects  of  the  sustenance  of  the 
nation.  Imports  from  oversea  had  been  restricted.  Meat, 
butter,  cheese,  and  fish  formerly  obtained  from  Holland  and 
Denmark  were  no  longer  available.  The  North  Sea  fisheries 
which  had  yielded  179,000  metric  tons  (1  metric  ton  = 
2200  lbs.)  of  fish  were  closed,  trained  farm  hands  were  fewer, 
crops  in  East  Prussia  and  Alsace  had  been  destroyed,  the 
situation  appeared  serious.  It  was  estimated  that  the  annual 
amount  of  food  fuel  necessary  to  support  68,000,000  Germans 
— men,  women,  and  children — was  56,750,000,000,000  calories. 
This  is  the  equivalent  of  3000  calories  per  adult  per  day.  The 
quantity  of  protein  required  in  this  fuel,  if  the  human  machines 
were  to  maintain  themselves  in  self-repair,  was  estimated  to 
be  1,605,000  metric  tons  per  annum.  It  was  calculated  that 
a  mixed  population  of  68,000,000  men,  women,  and  children 
required  the  same  amount  of  food  as  would  51,823,000  adults. 

In  order  to  increase  the  production  of  food  and  to  diminish 
the  waste  the  committee  recommended  increasing  the  crop  of 
beans,  with  its  large  protein  content,  reducing  the  unneces- 
sarily large  meat  supply,  and  increasing  the  intake  of  cheese 
and  skimmed  milk,  which  latter  should  no  longer  be  fed  to 
pigs,  improving  the  yield  of  vegetables  and  fruits,  and  reducing 
the  quantity  of  butter  and  cream  produced. 

1  The  first  pages  of  this  chapter  are  a  revision  of  a  paper  published  in  the 
"Journal  of  the  Washington  Academy  of  Sciences,"  1916,  vi,  387. 

555 


556 


SCIENCE    OF    NUTRITION 


A  reduction  in  the  consumption  of  meat,  butter,  and  cream 
was  necessary  because  edible  grains  would  be  required  for 
human  food,  and  the  maintenance  of  the  usual  number  of 
cattle  was  no  longer  deemed  possible. 

The  estimated  savings  as  above  enumerated  would  result 
in  a  total  production  of  81.25  billion  food  calories  containing 
2,022,800  tons  of  protein. 

The  conditions  were  thus  summarized : 

TABLE   SHOWING   THE   ANNUAL   FOOD   REQUIREMENTS   OF 
68,000,000  PEOPLE   IN   GERMANY 


Calories  in 
Thousand  Mil- 
lions. 


Actual  requirement 

Used  before  the  war ....    : 

Available  (unchanged  habits) 

Available  (under  present  recommendations) 


From  these  data  it  was  concluded  that  the  German  people, 
through  co-operation  of  millions  of  inhabitants,  would  be  able 
to  prevent  suffering  for  lack  of  food. 

The  writer  is  informed  upon  good  authority1  that  the  food 
produced  during  1914-16  never  attained  the  level  of  produc- 
tion in  peace  times,  that  the  food  requirement  of  the  popu- 
lation was  underestimated  for  the  physical  work  to  be  accom- 
plished and  underestimated  for  those  who  were  in  the  period 
of  adolescence;  furthermore,  that  the  enforcement  of  the  food 
laws  was  placed  in  the  hands  of  farmers,  middlemen,  and 
politicians,  who  mismanaged  the  situation. 

It  is  not  unimportant  to  know  something  of  the  cost  of 
these  great  quantities  of  food  fuel. 

If  one  takes  as  a  basis  the  wholesale  cost  in  the  United 
States  of  food  as  purchased  on  account  of  the  Commission  for 
Relief  in  Belgium  one  can  estimate  in  the  terms  of  the  cost 
of  various  simple  food-stuffs  the  lowest  wholesale  cost  of  the 
yearly  food  fuel  requirement  of  the  German  nation  as  follows: 

•A.  E.  Taylor:   Oral  communication,  quoted  by  permission. 


FOOD   ECONOMICS  557 

WHOLESALE    COST   IN    THE    UNITED    STATES    OF    FOOD    FUEL 
FOR   68,000,000   PEOPLE 


Cost  per 
Pound. 

Cost  per 

1000 
Calories. 

Cost  for 

56,750,000.000 
Calories. 

$0,016 
0.023 
0.03 
0-033 
0.045 

$0.01 1 
0.014 
0.018 
O.02 
0.029 

$    634,000,000 
794,500,000 

Wheat 

Rice 

1,022,500,000 

1,135,000,000 

1,634,000,000 

The  wholesale  cost  of  sufficient  food  fuel  exclusively  in  the 
form  of  beans  to  provide  for  100,000,000  men,  women,  and  chil- 
dren in  the  United  States  for  a  period  of  one  year,  computed 
on  the  basis  of  3000  calories  daily  for  each  adult,  would  call 
for  a  sum  of  $2,500,000,000.  Beans  are  more  costly  than  rice 
and  wheat,  but  have  a  larger  protein  content. 

In  this  connection  it  is  interesting  to  consider  the  living 
expenses  of  a  poor  family  in  New  York  City. 

Family,  two  adults,  three  children,  wages  $60  per  month: 

Rent $15.00 

Food , 25.00 

Coal 4.50 

Insurance 2.25 

Soap,  matches,  etc 1 .00 

Clothing  and  extras 12.25 

$60.00 

To  the  man  of  large  affairs  the  expenditure  of  $25  a 
month  for  food  appears  of  little  moment,  and  yet  if  the 
100,000,000  inhabitants  of  the  United  States  lived  as  this 
typical  poor  man's  family  lived  the  cost  of  food  would  aggre- 
gate $6,000,000,000  per  annum.  To  any  man  of  large  affairs 
the  maintenance  at  Boston  of  the  Nutrition  Laboratory  of  the 
Carnegie  Institution  with  its  budget  of  about  $50,000  per 
annum  appeals  impressively  to  the  imagination,  and  yet  this 
work  is  accomplished  at  an  expense  of  less  than  twih>  °f  I  Per 
cent,  of  what  the  American  people  would  pay  for  food  if  each 
family  of  5  had  an  income  of  $720  per  annum.  It  may  be 
further  remarked  that  this  estimated  cost  of  food  for  the 


558 


SCIENCE    OF   NUTRITION 


nation  is  twice  the  amount  of  the  gross  earnings  of  all  the 
railways  in  the  United  States. 

Is  it  not  a  little  sad  to  think  that  the  expenditure  of 
thousands  of  millions  of  dollars  annually  for  food,  an  expendi- 
ture frequently  amounting  to  more  than  half  of  the  income  of 
the  poor  man,  should  take  place  without  any  real  idea  as  to 
what  the  nature  of  food  is? 

F.  C.  Gephart1  of  the  Russell  Sage  Institute  of  Pathol- 
ogy, has  made  a  study  into  the  food  consumption  of  the  boys 
at  St.  Paul's  School  at  Concord,  New  Hampshire,  one  of  the 
largest  private  boarding-schools  in  the  country.  The  total 
annual  food  supply  may  be  thus  computed: 

SUPPLIES   FOR   BOYS'    BOARDING   SCHOOL 


Protein, 

Metric 

Tons. 

j 

Fat, 
Metric 
Tons. 

Carbohydrate, 
Metric 
Tons. 

Food  supply 1         20.5 

Waste : 3.8 

Food-fuel 16.7 

25.6 
5-4 

20.2 

60.5 
4.2 

S°-3 

This  quantity  of  nourishment  was  taken  by  355  boys  and 
also  about  ioo  adults  (masters  and  servants).  This  quantity 
of  food  when  computed  on  the  basis  of  the  individual  meals 
served  appears  as  follows: 


Food  Supply  per  Meal. 

Pounds. 

Grams. 

Calories, 

Calories 
Per  Cent. 

Protein 

O.I  107 
O.I332 
O.3717 

50.2 

60.4 

168.8 

206 
562 
692 

1460 

14* 

Fat 

39 

Carbohydrates 

47 

IOO 

*  70  per  cent,  of  this  is  in  animal  protein. 

The  cost  of  this  food  per  meal  was  20  cents,  or  13.8  cents  per 
1000  .calories.     The  food,  which  was  bought  by  a  purchasing 

1  Gephart:  "Boston  Medical  and  Surgical  Journal,"  1017,  clxxvi,  17. 


FOOD   ECONOMICS 


559 


agent  in  the  Boston  market,  was  of  the  best  quality,  and 
included  193  separate  varieties. 

Such  a  dietary  taken  by  the  100,000,000  inhabitants  of  the 
country  would  cost  per  annum  $11,500,000,000  if  the  Ger- 
man minimum  of  3000  calories  daily  per  adult  be  allowed. 
This  cost  is  twice  what  the  poor  man  in  New  York  City  pays 
for  his  food. 

These  growing,  athletic  boys,  however,  were  not  satisfied 
with  3000  calories  daily.  They  not  only  took  4350  calories 
daily  at  the  table,  but  they  bought  650  additional  calories  in 
food  at  a  neighboring  store,  the  principal  item  being  chocolate. 

Data  concerning  the  subjects  of  the  investigation  are 
epitomized  in  the  two  following  tables: 

TABLE    SHOWING   THE   NUTRITION   CONDITIONS  AT  A  SCHOOL 
CONTAINING   355   BOYS 


Average 
Age. 

Height. 

Weight. 

Body 
Surface. 

Basal 
Metab- 
olism 
(Calc). 

Food. 

Food  in 
Per  Cent, 
of  Basal. 

The  Upper 

School 

The  School. . .  . 
The  Lower 

School 

Years. 

16 
I4l 

132 

Cm. 

172.7 
165.1 

157-5 

Kg. 

60.6 
50.8 

43-8 

Sq.  M. 

i-73 
i-54 

1.40 

Cals. 

1826 
1737 

1647 

Cals. 

4997 

5126 

4949 

274 
295 

300 

The  basal  requirement  of  boys  is,  as  DuBois  (see  p.  129) 
has  shown,  25  per  cent,  above  that  of  the  adult.  The  total 
fuel  intake  was  three  times  that  of  this  basal  level  which  is  the 
heat  production  when  a  boy  is  resting  or  asleep.  The  5000 
calories  contained  in  the  ingesta  is  half  as  much  again  as  a 
farmer  at  work  would  require.  The  quantity  of  the  calculated 
intake  would  certainly  not  be  lowered  by  excluding  the 
adults  who  unavoidably  entered  into  this  computation.  These 
data  explain  the  ravenous  appetite  of  boys.  Lack  of  appre- 
ciation of  this  factor  or  lack  of  provision  for  it  are  the  probable 
causes  of  much  of  the  undernutrition  seen  in  children  of 
school  age. 


560  SCIENCE    OF   NUTRITION 

The  distribution  of  the  fuel  values  among  the  various 
more  common  articles  taken  as  food  at  the  school  is  shown  in 
the  following  table: 

PERCENTAGE  DISTRIBUTION  OF  THE  CALORIES  INGESTED  AT 
A   BOYS'   BOARDING   SCHOOL 

Per  Cent.  Per  Cent. 

Bacon 1.8  Lamb 5.3 

Beef 6.7  Milk 12.6 

Bread  and  flour 13.3  Pork  loins 1.1 

Butter n. 2  Potatoes 5.9 

Cream 1.3  Sugar 11.6 

Eggs 2.3  Other  items 24.5 

Fowl 1.9 

It  is  interesting  that  twelve  dietary  items  yield  75  per  cent, 
of  the  fuel  value  and  that  181  other  varieties  yield  the  remain- 
ing 25  per  cent.  Bread,  butter,  milk,  and  sugar  together  yield 
50  per  cent,  of  the  food  fuel. 

According  to  the  German  minimum  allowance  an  average 
family  of  5 — father,  mother,  and  three  children — would  require 
11,400  calories  in  food  daily.  If  the  family's  dietary  were 
based  proportionately  upon  that  of  the  boys'  school  it  would 
cost  as  follows,  provided  its  food  supplies  were  purchased  on 
Second  Avenue,  New  York  City: 

Calories.       Cost  in  Cents. 
Total  food 11 ,400 

Bread 1 ,500  5 

Butter 1,500  15 

Milk 1 ,500  16 

Sugar 1,500  4 

6,000  40 

Forty  cents  will  buy  more  than  half  the  family's  food  re- 
quirements at  an  average  cost  of  6|  cents  per  1000  calories 
instead  of  14  cents,  the  average  cost  at  the  school.  If  $25  is 
spent  each  month  for  food,  80  cents  a  day  is  available,  or  7  cents 
for  1000  calories.     The  margin  is  narrow. 

It  would  be  well  if  the  family  knew  that  more  than  half 
its  food  supply  could  be  had  for  40  cents  a  day,  and  that  this 
bread,  butter,  milk,  and  sugar  was  of  equal  nutritive  value  to 


FOOD    ECONOMICS 


56l 


the  best  the  country  affords.  The  remaining  5400  calories 
could  then  be  bought  at  a  cost  of  8  cents  per  1000.  This  sum 
will  purchase  most  of  the  usual  food-stuffs,  with  the  exception 
of  meat. 

As  a  matter  of  statistics  the  annual  consumption  of  cane- 
sugar  in  the  United  States  in  191 2-13  reached  85.4  lbs.  per 
capita,  which  is  the  equivalent  of  2000  calories  daily  for  a  family 
of  5,  or  20  per  cent,  of  the  energy  requirement.  This  quan- 
tity of  sugar  costs  the  nation  $1,500,000  daily,  and  the  rich 
harvest  to  be  reaped  by  substitution  of  only  a  small  part  of 
this  by  saccharin,  which  has  no  fuel  value  whatever,  is  obvious. 

It  has  appeared  to  those  at  work  in  the  laboratory  that  it 
would  be  of  great  importance  to  associate  the  caloric  value  of 
food  with  cost  in  dollars  and  cents. 

For  the  understanding  of  this  the  following  table  has  been 
prepared  showing  the  cost  of  2500  calories,  which  is  the 
energy  requirement  of  an  average  adult  of  sedentary  occupa- 
tion. 


WEIGHTS    AND    COSTS    OF  -  VARIOUS    FOODS    NECESSARY    TO 
FURNISH    2500   CALORIES 

(Prices  at  Second  Avenue  and  90th  Street,  New  York  City,  Early  in  1916) 


Articles. 


Cornmeal . 
Hominy.  . 
Oatmeal. . 


Weight.       Cost 


Lbs.  Oz. 


Flour 

Sugar 

Rice  (broken) .... 

Bread j  2 

Lard 

Corn  syrup 1  1 


Molasses 

Peanut  butter. 
Pork  (fat) .... 
Beans  (dried) . 
Oleoma  rgarin . 


5* 


5* 


9* 

13 


9 


Potatoes 8 


Cents. 

°4§ 

°42 

°5i 
06 

o6ff 

o7i 
o8i 
08^ 
09! 

1216 

14 

14 

14 

I5H 

.16A 


Articles. 


Dates 

Olive  oil 

Hickory  nuts 

(unhulled) 

Raisins  (dried) .... 

Apples  (dried) 

Cheese  (American 

pale) 

Butter 

Brazil  nuts 

(unhulled) 

Cocoa 

Lentils 

Almonds  (unhulled) 

Apples  (fresh) 

English  walnuts 

(unhulled) 

Cod  (salt) 


Weight.       Cost. 


Lbs.  Oz. 

1     12 

92 


13 


3 
11 


1    13 
6 


Cents. 
172 
19 

20 


26i 

24l6 

27 

29  -h 

30 

36 
38 

4IH 

00 


36 


562  SCIENCE   OF   NUTRITION 

True  food  reform  demands  the  sale  of  food  by  calories  and 
not  by  pounds.  Professor  Murlin  has  advocated  that  the 
government  compel  manufacturers  to  place  upon  each  can  or 
package  of  food  sold  the  caloric  content  of  the  package. 

Besides  fuel  value  it  must  be  remembered  that  the  body 
must  have  protein.  The  machinery  of  the  living  parts  of  the 
body  such  as  muscle  is  in  a  constant  state  of  wearing  away. 
The  wear  and  tear  is  slight,  but  protein  must  be  taken  in  the 
food  to  replace  that  destroyed  in  the  body,  or  the  machinery  of 
the  cells  will  wear  out  and  death  from  lack  of  protein  will 
ensue. 

Different  proteins  have  different  values  for  this  purpose. 
Those  of  meat,  fish,  eggs,  and  milk  will  replace  body  protein 
part  for  part.  Such  proteins  may  be  classified  as  proteins  of 
Grade  A.  Gelatin  has  practically  no  power  to  replace  body 
protein  and  should  be  classified  as  protein  of  Grade  D.  Wheat 
contains  a  mixture  of  proteins  of  Grades  A  and  D  in  which 
those  of  Grade  A  predominate,  so  wheat  may  be  classified  as 
having  a  protein  value  of  Grade  B,  whereas  corn,  from  anal- 
ogous reasoning,  may  be  said  to  have  a  protein  value  of 
Grade  C. 

An  ordinary  dietary  with  a  liberal  allowance  of  protein 
contains  15  per  cent,  of  its  calories  in  that  form.  A  can  or 
package  of  food  containing  15  per  cent,  of  its  calories  in  pro- 
tein should  have  a  star  placed  with  the  letter  determination 
of  the  grade  of  protein.  For  example,  the  label  on  a  can  of 
corn  should  read  "This  can  contains  x  calories,  of  which  y  per 
cent,  are  in  protein  of  Grade  C." 

A  further  desirable  statement  would  be  whether  or  not  the 
food-stuff  sold  contained  the  natural  mineral  constituents  from 
the  organic  source  from  which  it  was  derived. 

The  determination  of  the  heat  of  combustion  of  a 
dried  sample  of  food  takes  fifteen  minutes.  Probably  three 
hours  would  suffice  to  make  a  complete  analysis  by  a  gov- 
ernment expert.  The  manufacturer  should  send  his  sample 
to  the  Bureau  of  Chemistry  at  Washington,  declaring  that 


FOOD   ECONOMICS 


563 


to  be  his  standard,  and  requesting  information  regarding 
his  label.  He  should  pay  for  this  analysis  as  a  patentee 
pays  for  his  patent.  If  the  government  at  any  time  should 
find  the  manufacturer  selling  a  material  on  the  market  of  char- 
acter different  from  the  standard  deposited  with  the  govern- 
ment, the  manufacturer  should  be  heavily  fined. 

It  is  not  possible  to  consider  the  details  of  the  great 
amount  of  extremely  valuable  work  accomplished  by  the  scien- 
tific departments  of  the  Washington  Government  and  in  the 
individual  Agricultural  Experiment  stations  in  this  country 
and  abroad. 

It  may,  however,  be  of  interest  to  present  the  results  of  a 
study  of  the  sale  of  food  at  the  Childs  restaurants1  in  order  to 
show  this  principle  of  caloric  feeding,  now  adopted  in  hospitals 
and  upon  farms,  that  it  may  be  worked  out  in  the  daily  life 
of  the  people. 

THE  COST,  INCLUSIVE  OF  RESTAURANT  SERVICE,  OF  2500 
CALORIES  IN  FOODS  ARRANGED  IN  ORDER  OF  THEIR  IN- 
CREASING PRICE 

(Note  that  when  three  portions  furnish  2500  calories,  one  portion  affords 
a  good  meal.  When  nine  portions  furnish  2500  calories,  then  three  portions 
should  form  the  meal.) 


Name  of  Food. 


Napoleon 

Crullers 

Cabinet  pudding  and  vanilla  sauce 

Cocoanut  pie 

'A — Roast  beef  sandwich  with  roll .... 

Bath  buns 

Bread  custard  pudding 

Pineapple  pie 

Corn  muffins 

Apple  pie 

New  England  pudding  with  vanilla 
sauce 


Nutri- 
tional 
Calo- 
ries for 
Five 
Cents. 


453-6 

444 

399 

372 

357 

357 

355 

347 

342 

337 


330.7 


Per 

Cent. 

in 
Bread 

and 
Butter. 


Cost 
of 
2500 
Calo- 
ries. 


No.  of 
Orders 

to 
Make 
2500  Cal- 
ories. 


*  Contains  15  per  cent,  or  over  of  heat  in  protein.  "A"  contains  the  protein 
of  meat,  milk,  eggs,  or  cheese. 

1  Gephart  and  Lusk:  "Analysis  and  Cost  of  Ready-to-serve  Foods,"  pub- 
lished by  "American  Medical  Association,"  1915. 


564 


SCIENCE    OF    NUTRITION 


Name  of  Food. 


Nutri- 
tional 
Calo- 
ries for 
Five 
Cents. 


Per 

Cent. 

in 
Bread 

and 
Butter. 


Cost 
of 
2500 
Calo- 
ries. 


No.  OF 
Orders 

to 
Make 
2500  Cal- 
ories. 


Chocolate  spiced  cakes 

Walnut  layer  cake  with  marshmal 

low  icing 

Milk  crackers 

Bread  pudding  with  vanilla  sauce .  . 

Pumpkin  pie 

A — Lamb  croquettes  and  mashed  pota 

toes 

Coffee  cake 

Rhubarb  pie 

A — German  meat  cakes  and  French  fried 

potatoes 

Old-fashioned  molasses  cake 

Lemon  pie 

*A — Vienna  roast  with  French  fried  pota- 
toes   

Butter  cakes 

Minced  ham  sandwich 

Pork  and  Boston  beans 

Cornmeal   cakes   with   maple   cane 

syrup 

A — Ham  croquettes 

Cold  rice  pudding 

Ham  sandwich  with  roll 

Banana  layer  cake 

*A — Cream  chipped  beef  on  toast 

Cocoa 

*A — Roast  beef  cutlet  with  tomato  sauce. 
*A — German  meat  cakes  with  lyonnaise 

potatoes 

*A — Swiss  cheese  sandwich 

*  — Boston  baked  beans 

A — Vienna  roast,  spaghetti  and  potatoes 

Chocolate  cornstarch  with  cream  .  . 
Wheat  cakes  with  maple  cane  syrup 

Milk  crackers  and  milk 

*A — American  cheese  sandwich 

*  — New  York  baked  beans 

Hot  corn  bread 

*A — Country  sausage 

Indian  pudding  with  maple  sauce . 
*A — Minced  tongue  sandwich  with  tea 

biscuits 

Cream  roll 

A — Beef  cakes  with  brown  gravy  and 
macaroni « 

*  — New  York  beans,  on  the  side 

Graham  crackers 

A — Broiled  ham 

A — Roast  beef  hash,  browned 


324.0 

323-2 
3i7-i 

298.4 
296.1 

291.4 

290.2 


284.5 
281.9 
279.7 

278.3 
278.0 

277-3 
276.6 

275.2 
263.1 
263.1 
261.8 

253-4 
249.2 

247-5 
246.5 

246.4 
244.0 
240.3 
236.3 
231.6 

231-1 
230.5 
230.2 
229.7 
228.6 
227.7 
227.2 

225.6 
225.1 

224.8 
223.4 
223.3 
223.1 
222.1 


29-5 


27.2 


29.7 

63.8 
27.1 


32-7 


38.4 


59-6 
34-2 
34-o 


35-5 


35-i 


36-9 


•39 

•39 
•39 

.42 
.42 

•43 
•43 
•44 

-44 
•44 
•45 

•45 
•45 
■45 
•45 

•45 
•47 
•47 
.48 

•49 
•50 
•5° 
•5i 


•51 
•52 
•53 
•54 
•54 
•54 
•54 
•54 
•55 
•55 
■55 

•55 
•55 

•56 
•56 
•56 
•56 
•56 


3 
9 
9 

3 
9 
9 

3 
9 
9 
3 

5 

5 

9 

10 

10 

3 
10 

3 

3 
10 

5 

4 

n 

5 

5 

11 

5 
6 


FOOD   ECONOMICS 


565 


Name  of  Food. 


Oyster  pie ; 

-Minced  chicken  sandwich 

Apple  tapioca  pudding 

Potato  salad 

Chocolate  layer  cake 

-Breaded  veal  cutlet  and  tomato  sauce 

Egg-plant  fried  in  butter 

Buckwheat  cakes  with  maple  cane 

syrup 

-Roast  beef  croquettes  with  macarcni 
-Fried  bacon  with  French  fried  pota 

toes 

-Sardine  sandwich 

-Minced  ham  sandwich  with  olives. . 
-Ham  and  New  York  beans 

Vanilla  cornstarch  with  cream 

-Roast  beef  cutlet  and  mashed  pota- 
toes   

-Lamb  cutlet  and  mashed  potatoes 

Cocoanut  cake 

Cream  cheese  walnut  sandwich .  .  . 
-New  York  baked  beans  with  tomato 

sauce 

-Ham  and  Boston  beans 

-Liver  and  onions  with  French  fried 

potatoes 

-Beef  stew 

-Pork  and  New  York  beans .... 
-Ham  sandwich 

Rice  croquette  with  bacon .... 

Baked  apple  with  cream 

-Frankfurters  and  potato  salad. 
-Baked  beans  with  macaroni.  .  . 

Cup  of  coffee  (containing  cream  and 

sugar) 

-Mince  pie 

-Lamb  stew 

-Broiled  salt  mackerel  with  mashed 
potatoes 

Cherry  pie 

Pound  cake 

-Chicken  cutlet  and  mashed  potatoes. 
-Shredded  wheat  and  milk 

Cream  tapioca  pudding 

Soda  crackers  and  milk 

Strawberry  pie 

Chocolate  Eclair 

-Baked  lamb  pie  (individual) . . . 

-Corned  beef  sandwich 

-Broiled  bacon 


Nutri- 

Per 

tional 

Cent. 

Calo 

in 

RIES  FOR 

Bread 

Five 

and 

Cents. 

Butter. 

220.4 

220.3 

73-0 

217.2 

217.0 

38.4 

212.4 

21 1.9 

33-0 

208.7 

208.3 

208.3 

34-3 

208.I 

207.4 

206.8 

206.6 

40.2 

206.5 

205.7 

38.3 

205.4 

30-9 

204.6 

.... 

201.5 

201.5 

34-8 

201.3 

44.6 

200.1 

199.8 

35-3 

198.7 

38.5 

198.3 

73-2 

iq6.2 

43-4 

196.0 

195-9 

42.5 

195-8 

195-2 

1 94. 1 

193.6 

39-6 

192.2 

44.1 

I9I-5 

I9I-5 

191. 2 

57-6 

190  .8 

189.6 

188.6 

188.0 

188.0 

187.7 

46.6 

186.0 

79.1 

185.3 

34-3 

Cost 
of 

2500 
Calo- 
ries. 


No.  of 
Orders 

to 
Make 
2500  Cal- 
ories. 


$o.57 
■57 
■57 
•58 
•59 
•59 
.60 

.60 
.60 

.60 
.60 
.60 
.61 
.61 

.61 
.61 
.61 
.62 

.62 
.62 

.62 
•63 
•63 
•63 
.64 
.64 
.64 
.64 

.64 
.64 
•65 

•65 
•65 
•65 
.65 
.66 
.66 
.66 
.66 
.67 
.67 
.67 
.67 


4 
11 
11 

6 
12 

3 

4 

6 

4 

3 
12 
12 

4 
12 

4 
4 


6 
4 

3 
4 
4 
13 
4 
6 

4 
4 

13 
6 


3 
7 
7 
4 
7 

13 
7 
7 

13 
4 

13 
3 


566 


SCIENCE    OF    NUTRITION 


Name  of  Food. 


Rice  cakes  with  maple  cane  syrup.  . 

A— Cold  ham 

A — Roast  beef  croquettes  and  spaghetti 

*A — Chipped  beef  and  scrambled  egg.  .  . 

A — Minced  ham  with  scrambled  eggs .  . 

Peach  pie 

A — Baked  macaroni  and  cheese 

Huckleberry  pie 

French  toast  with  maple  cane  syrup 
*A — Corned  beef  and  New  York  beans.  . 

Blackberry  pie 

*A — Veal  pot-pie  with  dumplings 

*A — Creamed  codfish  on  toast 

A — Vienna  roast  with  stewed  tomatoes. 

*A — Tomato  omelet 

A — Small  oyster  fry 

Hot  rice  with  cream 

A — Plain  oyster  fry  with  bacon 

*A — Hamburger  steak 

A — Corned  beef  hash,  browned  in  pan. . 

A — Corned  beef  hash,  steamed 

Cream 

*A — Chicken  wings  on  toast 

A — Country  sausage  and  French  fried 

potatoes 

*A — Corned  beef  and  Boston  beans. . . 

*A — Two  fried  eggs 

*A — Ham  omelet 

*A — Plain  omelet 

*A: — Fried  liver  and  mashed  potatoes . 

*A — Creamed  chipped  beef 

A — Large  oyster  fry 

Apple  fritters  with  fruit  sauce .  .  . 
A — Fish  cakes  with  tomato  sauce. . . . 
French  fried  potatoes,  extra  order 
Chocolate  cornstarch  with  whipped 

cream 

Shredded  wheat  and  cream.  .  .  . 
A — Chicken  croquette  and  French  fried 

potatoes 

*A — Corned  beef  hash  with  poached  egg 

*A — Ham  and  eggs 

A — Ham  and  potato  salad 

*A — Baked  shad  and  dressing 

*A — Hamburger  steak  with  Spanish  sauce 

Charlotte  russe 

*A — Creamed  eggs  on  toast 

A — Bacon  and  eggs 

Strawberry  fruit  jelly  with  whipped 
cream 


Nutri- 

Per          r 
Cent.          c° 

tional 

Calo- 

IN                    ° 

ries  for 
Five 

Bread         -?, 
and           Ca 

.0- 

Cents. 

Butter. 

185.6 

'  .  .  . .          $0 

67 

183.5 

39-6 

68 

183.0 

68 

182.7 

36.4 

68 

'  181.Q 

35-5 

69 

181.8 

69 

181.6 

40.5 

69 

179.7 

7o 

179.2 

7o 

1 79. 1 

7o 

177-0 

7o 

174.0 

47-9 

7i 

174-7 

46.3 

72 

174-7 

31-3 

72 

174.4 

55-3 

72 

174.2 

36.6 

72 

173-3 

72 

171.8 

32.0 

73 

i7o-5 

29.9 

73 

170.3 

46.1 

73 

169.3 

55-8 

74 

168.7 

74 

168.2 

38.2 

74 

167.2 

75 

166.7 

48.6 

75 

166.0 

58.1 

75 

165.6 

35-5 

75 

165-5 

47.2 

75 

164.8 

5i-7 

76 

163-7 

5i-7 

76 

161. 8 

35-i 

77 

161. 7 

77 

161. 2 

54-4 

78 

160.4 

78 

159.6 

78 

159-5 

78 

159-3 

78 

158.9 

35-5 

79 

158.3 

29.8 

79 

158.1 

3i-i 

79 

157-7 

79 

157-4 

33-7 

79 

156.5 

80 

155-6 

37-6 

80 

155-3 

29.8 

81 

154-0 

81 

FOOD   ECONOMICS 


567 


Name  of  Food. 


*A — Buckwheat     cakes     with     country 

sausage 

A — Oyster  sandwich 

*A — Chicken  giblets  on  toast 

Hot  rice  with  butter 

Pimento  olive  cheese  sandwich 

*A — Liver  and  bacon  with  lyonnaise  po- 
tatoes  

*A — Corned   beef   hash,   browned,   with 

two  poached  eggs 

Buttered  toast 

*A — Liver  and  bacon 

*A — Chicken  hash 

A — Two  scrambled  eggs 

*A— Milk 

Apple  sauce  with  whipped  cream .... 

Hot  rice  with  poached  egg 

*A — Corned  beef  with  potato  salad 

Fish  cakes  with  poached  egg 

*A — Cold  roast  beef 

A — Hot  rice  with  milk .  . 

*A — Small  steak 

Baked  apple 

Baked  apple  with  ice  cream 

A — Two  lamb  chops 

A — Chicken  salad  sandwich 

*A — Corned   beef   hash,    steamed,    with 

poached  egg 

*   — Boston  beans,  on  side 

Tomato  sandwich 

A— Lamb  chops,  breaded,  with  mashed 

potatoes 

*A — Maple  flakes  with  milk 

*A — Corned  beef 

*A — Bulgarzoon 

A — Spanish  omelet  with   French   fried 

potatoes 

Baked  apple  custard  with  whipped 

cream 

Boiled  rice,  side  order 

*A — Fried  egg  sandwich 

*A— Onion  omelet 


*A — Baked  weak  fish  with  dressing.  .  .  . 
*A — Sirloin  steak 

Fresh  cooked  oatmeal  with  cream. 
*A — Fish  cakes  with  macaroni 

Sliced  bananas  with  cream 

*   — Macaroni,  side  order 

*A — Roast  sirloin  of  beef  and  mashed 
potatoes 


Nutri- 
tional 
Calo- 
ries for 
Five 
Cents. 


154-7 
153-8 
i53-o 
152.6 
152.3 

151.0 

150.1 
149.7 
149.4 
146.9 
146.3 

H5-3 
144.2 

143-3 
I43-I 
141.8 
140. 1 
139.6 
138.0 
136.8 
136.0 
135-3 
134-7 

133-8 
133-7 
133-6 

13^-7 
132.6 

132.4 
132-1 

132-1 

I3I-5 
130.8 
129.6 
129. 1 
128.9 
128. 1 
127.7 
126.9 
126.2 
125.8 

124.9 


Per 

Cent. 

in 
Bread 

and 
Butter. 


46.3 
41.5 

87.0 

29.7 

37-7 

36.4 
46.3 
52.6 


49.8 
53-i 
53-2 
63-4 

28.3 


44-3 
96.5 
48.6 

45 -S 

39-8 


64.7 
27.0 

45-o 
20.1 


44.8 


Cost 
of 
2500 
Calo- 
ries. 


No.  OF 
Orders 

to 
Make 
250c  Cal- 
ories. 


if. 


3 
6 
6 
9 
17 
6 
6 

4 
6 

9 

3 

18 

9 
3 
9 

5 
19 
19 

5 
9 
6 

19 


568 


SCIENCE   OF   NUTRITION 


\ auk  of  Food. 


A — Tomato  omelet  with  potatoes 

*A — Two  boiled  eggs 

*A — Fish  cakes  with  spaghetti 

*A — Macaroni  omelet  with  tomato  sauce. 

*A — Small  steak  with  onions 

*A — Fish  cake  sandwich 

*A — Egg  salad 

*A — Parsley  omelet 

Green  split  pea  soup 

Vanilla  ice  cream 

*A — Tenderloin  steak  with  onions 

*A — Cornflakes  and  milk 

Strawberry  tart 

*A — Tuna  fish  salad 

*  A— Sirloin  steak  with  onions 

Pineapple  fruit  jelly  with  whipped 

cream 

*A — Cup  custard 

*A — Roast  beef  with  potato  salad .  . 

*A — Tenderloin  steak 

A— Milk  toast 

Strawberry  cornstarch  with  whipped 
cream 

Strawberry  ice  cream 

*A — Clam  chowder 

*  — Chicken  soup 

*A — Crab  meat  salad 

Vegetable  soup 

Stewed  rhubarb 

*A — Creamed  chicken  on  toast 

Strawberries  with  cream 

Strawberry  short  cake 

*A — Chicken  omelet 

*A — Deviled  crab 

Sliced  bananas 

*  A— Spaghetti  and  cheese 

*A — Fried  ham 

A — Minced  chicken  sandwich  with  let- 
tuce  

*  —Bean  soup  with  croutons 

*A — Hot  roast  beef  sandwich 

*A — Club  sandwich 

*A — Sliced  chicken  sandwich 

*A — Poached  eggs  on  toast 

Strawberries  with  ice  cream 

*  — Cream  of  wheat 

Blackberries  and  cream 

Stewed  corn 

*  — Creamed  asparagus  on  toast 

Watermelon 


NUTRI-               ] 

'kr 

r-          C°ST 

TIONAL            C 

EN 

Calo- 

IN 

ries  for      B 
Five            j 

■(LA 
N'l 

D        Calo- 

Cents.       Bu 

IT] 

R.            RIES- 

121.9          4 

2-C 

>               $1.03 

121. 6 

I.03 

120.6          5 

4.c 

)                   I.O4 

119. 1          3 

8.« 

I.05 

118.3          2 

§•' 

;        1.06 

117.8 

1.06 

116.0         5 

4-t 

>        1.08 

"5-2         5 

3-> 

1.09 

114.1         5 

gu 

[        1. 10 

113.8 

1. 10 

H3-3         2 

4-! 

1. 10 

in. 1 

1. 12 

III.O 

1.13 

1 10.9         4 

3-< 

>        1. 13 

IIO.O             2 

0.] 

1. 14 

IO9.8 

1. 14 

IO9.5 

1. 14 

107.4         4 

3-c 

.        1. 16 

106.3         I 

9-i 

5           1. 18 

105.6 

1. 18 

102.2 

1.22 

102. 1 

1.22 

100.6 

1.24 

100.4         4 

9-.[ 

1.24 

99-5         6 

S.i 

1.26 

98.1          7 

9.( 

>        1.27 

93-9 

i-33 

92.9         3 

7-! 

i-3S 

91.9 

1.36 

91.8 

1.36 

90.8         3 

2.] 

1.38 

90.7         6 

4.1 

1.38 

89.9 

i-39 

88.0 

1.42 

86.8        4 

9.t 

1.44 

86.3 

i-4S 

84.4 

1.48 

81.5         • 

i-53 

81.4 

i-S4 

78.1 

1.60 

65.6 

1.91 

65.0 

1.92 

63.0 

1.98 

56.5 

2.21 

52.5 

2.38 

49.2 

2-54 

39-4 

3-17 

No.  of 
Orders 

TO 

Make 
2500  Cal- 
ories. 


FOOD   ECONOMICS 


569 


Name  of  Food. 


*  — Tomato  soup  with  rice 

Sliced  pineapple 

Grapefruit 

*A — Raw  oysters 

Sliced  tomatoes  with  lettuce. . . . 

*  — Sliced  tomatoes 

Tomatoes  with  lettuce  dressing. 

Cantaloupe 

Champagnef 


Nutri- 
tional 
Calo- 
ries for 
Five 
Cents. 

Per 

Cent. 

IN 

Bread 

and 
Butter. 

36.6 

35-3 
25.8 
18.6 
16.6 
is-2 
i3-5 
12. 1 
8.6 

Cost 
of 
2500 
Calo- 
ries. 


*3-42 
3-54 
4.85 
6.72 

7-53 

8.20 

9.26 

10.33 

14-53 


No.  OF 
Orders 

to 
Make 
2500  Cal- 
ories. 


34 
7i 
32 
45 
50 
82 
47 
69 


t  Not  purchased  in  the  restaurant. 


The  main  objection  that  has  been  encountered  to  the  sale 
of  food  on  the  caloric  basis  has  been  the  sensitiveness  of  the 
business  world  to  the  introduction  of  a  new  and  unknown 
quantity.     Why  not  leave  well  enough  alone? 

A  more  highly  educated  generation  will,  however,  demand 
that  its  expenditure  of  thousands  of  millions  of  dollars  for  food 
shall  not  continue  to  take  place  in  unfathomable  depths  of 
darkness. 

For  the  purpose  of  dealing  with  the  unintelligent  masses  in 
actual  need  of  food  the  writer  recommended  to  Dr.  Haven 
Emerson,  the  local  Commissioner  of  Health  in  New  York  City, 
that  grocers  be  persuaded  to  prepare  "Board  of  Health 
baskets"  to  provide  10,000  calories  daily  for  a  family  of  5 
at  a  minimum  cost.  The  occasion  was  that  of  a  general  strike 
in  the  cloak-making  trade.  The  baskets  were  reminiscent  of 
the  poorhouse  fare  in  Finland  (see  p.  351)  and  should  be  un- 
derstood as  representing  minima  for  a  family  out  of  work. 
Basket  I  is  not  to  be  commended  for  constant  use  over  a 
prolonged  period,  though  Basket  II  would  probably  suffice 
for  maintenance  and  growth  during  many  months. 


57° 


SCIENCE    OF   NUTRITION 
HEALTH   BASKETS 


(Low  cost  meatless  dietary  for  a  family  of  5 — two  adults  and  three  children 
over  five  years — designed  to  maintain  efficiency  for  one  day,  June,  1916) 


Articles  Arranged  in  the 
Order  of  Increasing  Cost 

Basket  I. 
Possible  Minimum. 

Basket  II. 
Desirable  Minimum. 

or  Fuel  Value. 

Pounds. 

Calories. 

Cost. 

Pounds. 

Calories. 

Cost. 

Cornmeal 

i) 

I 

,1* 

z4 

A 
3 

1 
2 

4t 

175° 

1800 

2800 
500 

1800 
1270 

9920 

•03 
.08 

.09 

.02 

.11* 

.12 

■455 

1 

I 

2\ 
\ 

1 
2 

3l 

4 
2 

I750 
1800 

2800 
500 

1800 

IOOO 

1270 

500 

Hominy 

Oatmeal 

•°3 

Sugar 

Rice 

.08 

Bread 

.09 
.02 

Corn  syrup  or  molasses. 
Pork  (fat) 

Beans  (dried) 

Oleomargarin 

■  III 

Potatoes 

.10 

Milk 

.12 

Apples 

.10 

11,420 

.65! 

*  Three  loaves  of  12-ounce  day-old  bread,  3  cents  a  loaf.  Rice,  i|  pounds 
(2625  calories)  costs  7§  cents  and  may  in  part  be  used  instead  of  bread. 

t  Two  quarts  of  milk  at  6  cents  a  quart. 

Notes  on  preparation  of  food: 

Oatmeal  contains  valuable  iron  and  calcium  salts.     Boil  one-half  hour. 

Hominy. — Soak  in  water  over  night.     Boil  one  and  one-half  hours. 

Cornmeal. — Boil  one-half  hour. 

Rice. — Twenty-five  minutes'  rapid  boiling. 

Potatoes.— Boil  one-half  to  three-quarters  of  an  hour. 

Beans. — High  in  protein  and  calcium.  Soak  over  night  and  boil  two  to 
two  and  one-half  hours. 

Rubner1  has  set  forth  his  ideas  of  true  reform  with  regard 
to  the  question  of  the  nourishment  of  the  masses.  There 
should  be  less  profit  to  middlemen.  If  food  must  be  eaten 
outside  the  home,  there  should  be  cheap  restaurants  or  public 
kitchens  where  nourishing  food  can  be  purchased.  It  is 
cheaper  to  cook  in  one's  own  kitchen  provided  the  fire  that 
is  used  for  cooking  is  needed  for  heating.  The  personal  owner- 
ship of  a  house  and  garden  to  the  wide-spread  extent  of  such 
ownership  in  America  must  be  morally  uplifting  for  a  com- 
munity.     For  this   reason   factories  should  be  built  in  the 

1  Rubner:    "Wandlungen  in  der  Volksernahrung,"  Leipzig,  1913. 


FOOD   ECONOMICS  ,  57 1 

country.  Furthermore,  children  are  more  useful  in  the  coun- 
try than  in  the  city.  The  cost  of  rooms  in  which  to  live  bears 
an  intimate  relation  to  the  amount  of  money  available  for 
food.  Not  only  are  quarters  costly  in  the  town,  but  many 
landlords  classify  children  with  cats  and  dogs  as  undesirable 
tenants. 

The  housewife  should  know  about  cooking,  and  both  she  and 
her  husband  should  know  something  of  the  value  of  food.  The 
sum  wasted  for  alcoholic  beverages  would  frequently  be  suffi- 
cient to  turn  the  scale  in  favor  of  the  proper  nutrition  of  the 
family.  Cheaper  milk  for  the  babies  of  the  poor  and  adequate 
nourishment  for  school  children  are  important  factors  in  the 
situation.  Rubner  regrets  that  the  knowledge  of  biology, 
even  among  the  educated  classes,  is  so  limited  that  the  science 
of  nutrition  appears  to  them  to  be  wholly  useless. 

Rubner's  words  were  written  in  contemplation  of  a  highly 
developed  modern  community  and  before  the  outbreak  of  the 
war.  The  story  of  the  regulation  and  conservation  of  the  food 
supply  by  the  state  under  scientific  direction  is  yet  to  be  writ- 
ten. An  enforced  abstinence  from  alcohol  cannot  possibly  be 
harmful,  but  whether  the  introduction  each  week  of  two  or 
three  "meatless  days"  into  the  regimen  of  adults,  and  espe- 
cially of  children,  is  for  their  permanent  welfare  cannot  at 
present  be  determined.  The  psychologic  factor  alone  is  of 
too  profound  significance  to  give  credence  to  the  value  of  any 
personal  opinion. 

As  this  book  goes  to  press  it  seems  that  America  herself 
is  certain  to  face  a  food  shortage  before  very  long.  This  can 
be  remedied  by  increasing  the  number  of  milch  cows  and  by 
reducing  the  livestock  raised  for  meat.  The  latter  would  free 
arable  land  for  the  production  of  grain  and  potatoes  and  save, 
for  human  consumption,  grain  fed  to  steers.  It  is  quite  certain 
that  meat  in  the  quantity  it  is  consumed  today  is  entirely  un- 
necessary, and  it  is  susceptible  of  scientific  proof  (see  p.  312) 
that  mechanical  work  is  more  efficiently  and  economically 
derived  from  carbohydrate  food  than  from  meat. 


APPENDIX 


Fig.   28.— Thermometer  showing  comparison  of  Fahrenheit  and  Centigrade 

scales. 

573 


574 


SCIENCE    OF    NUTRITION 


CONVENIENT    COMPARISONS    OF    METRIC    AND    AVOIRDUPOIS 

WEIGHTS 

i  kilogram  =       2.2046  pounds 

1  pound  =  453.6        grams 

1  ounce  =  28.3        grams 

1  liter  =  61.027    cubic  inches  =  1.7608  pints 

1  gram-calorie  =      0.425    kilogram-meters  of  mechanical  energy 

1  meter  =       3.2809  feet 

i  kilometer  =      0.6214  miles 


THE  CHEMICAL  COMPOSITION  OF  NORMAL  URINES  ON  PURIN- 
FREE  DIETS.     (After  Folin,  see  p.  209.) 


Total  N  in  grams 

UreaN 

Ammonia  N 

Creatinin  N 

Uric  Acid  N 

Undetermined  N 

Total  S03  in  grams 

Inorganic  S03 

Ethereal  S03 

Neutral  S03 

In  per  cent,  of  total  N: 

UreaN 

Ammonia  N 

Creatinin  N 

Uric  Acid  N 

Undetermined  N. . . . 

In  per  cent,  of  total  SO3: 

Inorganic  S03 

Ethereal  SO3 

Neutral  S03 


E.  S.  A. 


June. 


29th         30th 


14.6 

12.6 
0.54 
0.39 
O.I5 
O.96 

3.02 
2.56 
O.26 
0.20 


86.O 

3-6 
2.7 
1 .0 
6.6 


34.7 
8.6 
6.7 


15.8 
13-9 
o.54 
0.43 
0.11 
0.88 

2.94 
2.58 
0.22 
0.14 


87.7 

3-3 
2.7 
0.7 
5-6 


87.7 
7-4 
4-9 


H.  B.  H. 


March. 


Sth  9th  10th 


15-9 

13-5 
0.41 
O.70 
O.26 
I.06 

3-°3 
2.48 
O.20 
o-35 


84.7 
2.6 
4.4 
1.6 
6.7 


81.8 

6.6 

11.6 


15-5 
13-4 
0.41 
0.64 
0.23 
0.79 

2.49 
2.05 
0.18 
0.26 


86.4 
2.7 
4.1 
i-7 
5-i 


82.0 

7-2 

10.8 


15.0 

12.9 

0.43 
0.69 
0.27 
0.68 

2.19 

i-74 
0.19 
0.26 


86.2 
2.9 
4.6 
1.8 
4.4 


79-4 
8.6 


July. 


13th        20th 


16.8 

14.7 
0.49 
0.58 
0.18 
0.85 

3-64 
3-27 
0.19 
0.18 


87-5 
3-° 
3-6 
1.05 
4.85 


90.0 
5-2 
4.8 


3-6 

2.2 

0.42 

0.60 

0.09 

0.27 

0.76 
0.46 
0.10 

0.20 


61.7 

"•3 

17.2 

2-5 

7-3 


60.5 
13.2 
26.5 


YEAR  OF   1905 
TABLE  SHOWING  THE  COST  OF  PROTEIN  AND  ENERGY 

As  Furnished  by  a  Number  of  Common  Food  Materials,  at  Prices  Current  in  the  East- 
ern Part  of  the  United  States 

Compiled  by  Langworthy,  U.  S.  Department  of  Agriculture,  1Q05.  in  Farmers'  Bulletin, 

Xo.  85,  p.  19. 

Note  that  the  prices  for  1917  are  double  or  triple  those  given  here.     Compare  with  prices  of 

1915  on  p.  561. 

(1  pound  =  453-6  grams.) 


Kind  of  Food  Material. 


Codfish,  whole,  fresh 

Codfish,  steaks 

Bluefish 

Halibut 

Codfish,  salt 

Mackerel,  salt 

Salmon,  canned 

Oysters  (solids,  30  cents  quart) 
Oysters  (solids,  60  cents  quart) 

Lobster 

Beef,  sirloin  steak 

Beef,  sirloin  steak 

Beef,  round 

Beef,  stew  meat 

Beef,  dried,  chipped 

Mutton  chops,  loin 

Mutton,  leg 

Pork,  roast,  loin 

Pork,  smoked  ham 

Milk  (7  cents  quart) 

Milk  (6  cents  quart) 

Wheat  flour 

Corn  meal 

Potatoes  (90  cents  bushel) 

Potatoes  (45  cents  bushel) 

Cabbage 

Corn,  canned 

Apples 

Bananas 

Strawberries 


c 
z 
B 

0 

0- 

a. 

3 
fx  O 

0 
<  . 

u  > 
,  ° 
0  a 
0  ta 

°z 

Amounts  for  10  ( 

H 

B 

% 

r-^ 

l» 

>  c  « 

w 

H 

O 

O 

■r.  os 

<  i  < 

Ch 

u 

0 

0 

S3 

Ph 

Cents. 

H 

Dollars. 

Cents. 

Lbs. 

Lb. 

IO 

O.OO 

48 

I. OOO 

O.III 

12 

•71 

36 

•833 

.142 

12 

I.20 

s« 

•833 

.083 

18 

1. 18 

40 

.556 

.085 

7 

•44 

23 

I.429 

.229 

10 

.61 

10 

I. OOO 

.163 

12 

.62 

18 

•833 

.162 

15 

2.50 

68 

.667 

.040 

30 

5.00 

136 

•333 

.020 

18 

3-05 

129 

•556 

•033 

25 

1.52 

26 

.400 

.066 

20 

1. 21 

21 

.500 

.083 

14 

•74 

16 

.714 

.136 

5 

•3« 

5 

2.000 

.266 

25 

•95 

33 

.400 

.106 

20 

1.48 

14 

.500 

.068 

22 

1.46 

25 

•454 

.069 

12 

.90 

10 

•833 

.112 

22 

i-S5 

14 

•454 

.064 

3 

1.06 

n 

2.857 

.094 

3 

.91 

10 

3-333 

.IIO 

3 

.26 

2 

3-333 

.380 

2 

.22 

1 

5.000 

.460 

th 

•8.3 

5 

6.667 

.120 

4 

•42 

2 

^3-333 

.240 

2i 

1.79 

21 

4.000 

.056 

10 

3-57 

23 

1. 000 

.028 

i* 

5.00 

7 

6.667 

.020 

7 

8-75 

24 

1.429 

.Oil 

7 

7.78 

42 

1.429 

•OI3 

209 

274 

172 

253 

437 
998 
547 
147 
74 
77 
380 

475 

615 

1862 

3°3 
694 

394 

1016 

729 

891 

1040 

5363 

8055 

2020 

4040 

484 

444 

1420 

414 

240 


575 


576 


SCIENCE    OF    NUTRITION 


A  more  extensive  compilation,  which  permits  not  only 
the  calculation  of  the  nutritive  value  of  the  particular  edible 
food  but  also  of  the  approximate  weight  of  inedible  waste 
entailed  in  the  direct  purchase  of  the  material  in  the  market, 
is  as  follows : 

COMPOSITION  OF  ORDINARY  FOOD  MATERIALS 

According  to  Atwater  and  Bryant. 
Report  of  the  Storrs  Agricultural  Experiment  Station,  1890,  p.  113,  somewhat  abridged. 


Kind  of  Food  Material. 


—  .2 


0i~3 


Edible  Portion. 


Available  Nutrients. 


>  i; 


o     • 

>5  5E 


Animal  Foods. 
Beef  (fresh). 

Brisket 

Chuck 

Flank 

Loin,  lean 

Loin,  medium 

Loin,  fat 

Neck 

Plate 

Ribs 

Round,  lean 

Round,  medium 

Round,  fat 

Round,  second  cut 

Rump 

Fore  shank 

Tongue 

Shoulder  and  clod 

Fore  quarter 

Hind  quarter 

Side,  lean 

Side,  medium 

Side,  fat 

Liver 

Suet  (unrendered  tallow) 
Hind  shank 


Beef  (preserved  and 
cooked). 

Dried  and  smoked 

Brisket,  corned 

Flank,  corned 


% 
23-3 
16.3 
10.2 

131 

13-3 
10.2 
27.6 
16.S 
20.8 
8.1 
7.2 
12.0 

iQ-5 

20.7 

36.9 
26.5 
16.4 
18.7 
15-7 
19-5 
17.4 
13.2 


53  -9 


4-7 
21.4 


°7 

54-6 
62 
60 
67 

no 


54-3 
50.0 
49.9 


% 
2.1 
1.8 
1.9 
1.2 


2.0 
1.0 
1.6 
1.6 

i-3 
2.0 

i-4 
1-3 
i-5 


i-3 
1.8 

2-5 

1.2 

4-3 
i-4 


3-5 


% 
15-3 
17.9 
18.3 
19. 1 
17.9 
17.0 

19-5 
16.0 
17.0 
20.7 
10.7 
18.9 
19.8 
16.9 
19.8 
18.3 
19.0 
17.4 
17.8 
18.7 
17.6 
15-7 
20.4 
4.6 
20.3 


29.1 
17.8 
14.2 


% 
27.1 
17. 1 
19.9 
12. 1 
19.2 
26.2 

15-7 

27.6 

2  5-3 

7-5 
12.9 
18.5 

8.2 
24.2 
11 .0 

8.7 
10.7 
20.3 
20.5 
12.5 
20.9 
34-6 

4-3 
77-7 
10.9 


6.2 
23-5 
3i-4 


% 


% 
7 
7 
7 
o 
8 
9 
7 
6 


6.8 

4-2 


Calo- 
ries. 

1475 
I095 
1225 

900 
1185 
1470 
1065 
1510 
1430 

735 

950 
ii75 

75o 
1380 

865 

740 

840 
1220 
1240 

910 
1250 
1805 

620 
3440 

875 


850 
1370 
1635 


APPENDIX 


577 


COMPOSITION  OF   ORDINARY   FOOD   MATERIALS    (Continued) 


Kind  of  Food  Material. 


Edible  Portion. 


Available  Nutrients. 


SZ 


"3     ■<°'  m 

3   Q,  II  O 


Animal  Foods. 

Beef  (preserved  and 

cooked) . 

Plate,  corned 

Rump,  corned 

Canned,  boiled 

Canned,  corned 

Boiled  beef  (cut  not  given) 

Roast,  cooked 

Loin  steak,  cooked 

Tripe,  pickled 


14-5 
6.o 


Veal  (fresh). 

Breast 21.3 

Chuck 18.9 

Cutlets  (round) 3 .4 

Flank 

Leg 14 

Loin 16.5 

Neck 3!-5 

Rib 24.3 

Shank 62.7 

Fore  quarter 24.5 

Hind  quarter 20.7 

Side 22.6 

Liver 


Lamb  (fresh). 

Breast  or  chuck iq.i 

Leg 17-4 

Loin 14.8 

Neck 17.7 

Shoulder 20.3 

Fore  quarter 18.8 

Hind  quarter 15.7 

Side :  19.3 


Lamb  (cooked). 

Chops,  broiled 13.5    47.6 

Leg,  roast 67.1 


Mutton  (fresh). 

Chuck 21.3 

Flank 9.9 

37 


/o 

40 
58 
51 
5i 
38 
48 
54 


66.0 

73  -o 
70.7 
68.9 
70.0 
"69.0 
72.6 
72.7 

74-5 
71.7 
70.9 
7i-3 
73  -o 


% 


i-5 

1 .1 

i-3 
i-3 
1-3 
i-3 


1.0 

1 .2 


1.2 

•9 


2.2 
1.9 


SO-9 
46.2 


2.4 
2.6 


75 

% 

13-3 

39-8 

14.8 

22.1 

24.7 

21.4 

25-5 

17.8 

25-4 

33-2 

21.6 

27.2 

22.S 

19.4 

1 1 -3 

1.1 

18.9 

*3-3 

rg.i 

6.2 

19.7 

7-3 

19.9 

9.9 

19.6 

8.6 

i9-3 

10.3 

19.7 

6.6 

20.1 

5-8 

20.1 

4-4 

19.4 

7.6 

20.1 

7-9 

19.6 

7-7 

9-7 

5-o 

18.5 

22.4 

18.6 

15-7 

18. 1 

26.9 

17.2 

23.6 

17.6 

28.2 

17.8 

24-5 

19.0 

18. 1 

17. 1 

21.9 

21.0 

28.4 

19. 1 

12. 1 

14.6 

3i-9 

14.7 

36.4 

% 

3-5 
2.8 
1.0 
3-o 

•7 
1.0 

■9 


1.0 
.6 


Calo- 
ries. 
1980 
1250 
1415 
1275 
1930 
1410 
1290 
2  75 


95° 
650 
71O 
82S 
760 
830 
680 
650 
S90 
715 
740 

725 
410 


1335 
IO50 
IS20 
1360 

1565 
1410 
1 160 
1285 


1640 
9°5 


1665 
i860 


578 


SCIENCE    OF    NUTRITION 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued) 


Kind  of  Food  Material. 


Oi-V 


Edible  Portion. 


Available  Nutrients. 


—  b  i^« 


Animal  Foods. 

Mutton  (fresh). 

Leg 

Loin 

Neck 

Shoulder 

Fore  quarter 

Hind  quarter 

Side 


Mutton  (cooked  and 
canned). 

Leg,  roast 

Corned,  canned 

Tongue,  canned. 


Pork  (fresh). 
Chuck,  ribs  and  shoulder. 

Flank 

Loin,  chops 

Ham 

Shoulder 

Side 


Pork    (pickled,    salted,  and 
smoked). 

Bacon 

Ham 

Shoulder 

Salt,  lean  ends 

Salt,  fat 

Pigs'  feet,  pickled 

Pork  (cooked). 

Ribs,  cooked 

Steak,  cooked 


Bologna . 
Frankfort. 
Pork 


Sausage. 


Poultry  and  game  (fresh). 

Chicken,  broilers 

Fowl 

Goose 

Turkey 


% 
18.4 
16.0 
27.4 

22.5 
21  .2 
17.2 


18.O 

IQ-7 
IO.7 
12.4 

"•5 


7-7 
13.6 


35-5 


3-3 


41.6 

25-9 
17.6 
22.7 


% 
62.8 
50. 2 
58.1 
61.9 
52-9 
54-8 


18.8 

4- 

40.3 

3- 

45 -o 

3- 

19.9 

5- 

7-9 
68.2 

5- 
1. 

33-6 

33-2 

60.0 

57-2 
39-8 

74.8 

63-7 
46.7 

55-5 


% 
1-7 
2.4 
2.0 

i-7 

2.2 
2.1 


54-2 

2.1 

50.9 

2.1 

45-8 

3-° 

47.0 

3-i 

5i-i 

2-3 

59  -o 

1.9 

52.0 

2.2 

53-9 

2.1 

51-2 

2-3 

34-4 

3-2 

3-i 
3-3 


2.4 

2-3 

3-i 


1.0 

1.6 

2-5 
1.9 


% 
17.9 

i-55 
16.4 
17.2 

i5-i 
16.2 
15.8 


24-3 
27.9 

23-7 

16.8 
17.9 
16. 1 
14.8 
12.9 


9.6 

15-8 

15-4 

8.1 

1.8 

15.8 


24.1 
19-3 


18.1 
19.0 
12.6 


20.9 
18.7 
15.8 
20.5 


% 
17. 1 

3i-4 
23-4 
18.9 
29.4 
26.7 
27-5 


21-5 

21.7 

22.8 


29-5 

21. 1 

28.6 

27-5 
32-5 
52.5 


64.0 
36.9 
3°-9 
63-7 
81.9 
14. 1 


35-7 
43-i 

16.7 
17.7 
42.0 


2.4 
15-5 
34-4 
21.8 


% 


°-3 


% 
8 
6 

7 
7 
7 
6 

7 


•9 
3-2 
3-6 


3-3 
3-6 
S-o 

4-3 
2.9 

•7 


i-7 


APPENDIX 


579 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued) 


Kind  of  E.ood  Material. 


Animal  Foods. 

Poultry  and   game    (cooked 

and  canned). 

Capon 

Turkey,  roast 

Plover,  roast,  canned 

Quail,  canned 


Fish  (fresh). 
Bass,  black,  whole.  . 

Bluefish 

Codfish,  dressed.  .  .  . 

Cod  steaks 

Flounder,  whole.  .  .  . 

Haddock 

Halibut  steak 

Lake  trout 

Mackerel 

Weakfish 

Whitefish,  whole. . . . 


Shell-fish  (fresh). 
Long  clams,  in  shell. . 
Round  clams,  in  shell . 

Oysters,  in  shell 

Oysters,  solids 

Clams,  round,  solids.  . 

Crabs,  hard  shells 

Lobster 


Fish  (preserved  and 
canned). 

Cod,  salt 

Cod,  salt,  boneless 

Halibut,  smoked I    7.0 

Herring,  smoked 44-4 

Mackerel,  salt,  dressed.  .  .  .    19.7 


as 

.2  J3 


10.4 


54-8 
48.6 

76 
78 

29.9 

58 

9.2 
61.5 

79- 
84. 

51.0 

Si. 

17-7 
48.5 

75- 
70 

44-7 

73 

51-9 
53-5 

79 
69 

41.9 

67.5 

81.4 


524 

61.7 


24.9 

1.6 


Salmon,  canned. 
Sardines,  canned 
Lobster,  canned. 
Clams,  canned. . . 
Oysters,  canned. . 


14.2 
5-o 


Edible  Portion. 


% 
59-9 
67-5 
57-7 
66.9 


85.8 
86.2 
86.9 
88.3 
80.8 
77.1 
79.2 


c  5 


% 

1.7 

i-3 
1-7 
1.6 


.6 
1.0 
1.4 
1 .1 


6.8 
5-5 
5-o 
5-2 
5-o 
1.9 
3-i 
i-3 


Available  Nutrients. 


c 

£ 

Ph 

Uh 

/o 

% 

26.2 

10.9 

17. 1 

10.9 

21.7 

9-7 

21  .1 

7-6 

20.0 

1.6 

18.8 

1.1 

IO.8 

.2 

l8. 1 

•5 

13-8 

.6 

16.7 

•3 

18.0 

4-9 

17-3 

0.8 

18.1 

6.7 

17-3 

2-3 

22.2 

6.2 

8-3 

•9 

6-3 

•4 

6.0 

1.1 

*2  2 


10.3 
16. 1 
15-9 


20.9 
24.9 
20.1 
35-8 
16.8 
21. 1 
22.3 
17.6 
10.2 
8-5 


1.2 

1 .0 
1.9 
i-7 


■3 

■3 

14-3 

15.0 

25--I 

18.7 

1.0 

.8 

2-3 


% 


1.6 


2.0 
4.2 
3-7 
3-3 
5-2 
1.2 


% 
1 .0 

2.4 
7-6 


2.0 

2.0 

1-5 

.8 

i-7 

2-3 

i-7 


18.5 
14-3 
"•3 
9.9 

9-7 
2.0 
4-2 
1.9 
2.1 
I.I 


.HO 


Calo- 
ries. 

995 

855 
985 
780 


470 
420 

225 
385 
300 

345 
57o 
765 
650 

445 

710 


240 
215 
235 
225 
340 
425 
400 


430 

5io 

1015 

1360 

1415 

915 

1250 

400 

200 

340 


580  SCIENCE    OF    NUTRITION 

COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued) 

Edible  Portion. 


Kind  of  Food  Material. 


, 

3 

0*  — 

O  £ 

&rt 

3S 

aS~ 

-Q.fi 

rt 

* 

Available  Nutrients. 


—  cd 

1-     I- 

rtT3 


Animal  Foods. 

Eggs,  uncooked 

Eggs,  boiled 


Dairy  products,  etc. 

Whole  milk 

Skimmed  milk 

Condensed     milk,     sweet- 
ened   

Cream 

Cheese 

Butter 

Oleomargarin,  etc 

Lard,  cottolene,  etc 

Animal  Foods. 
Miscellaneous. 

Gelatin 

Calf  s-foot  jelly 


/o 


Vegetable  Foods. 
Cereals,  etc. 

Barley,  pearled 

Buckwheat  flour 

Buckwheat,  self-raising. . .  . 

Corn  (maize)  flour 

Corn  (maize)  meal 

Corn  (maize)  preparations 

Cerealine 

Hominy 

Hominy,  cooked 

Oatmeal  and  rolled  oats .  .  . 

Oatmeal,  boiled 

Rice 

Rice,  boiled 

Rye  flour 

Entire  wheat  flour 

Gluten  flour 

Graham  flour 

Wheat  flour,  patent  proc- 
ess: 

Low  grade 

Bakers'  grade 


/o 

73-7 
73-2 


87.0 
90.5 

26. 9 
74.0 
34- 2 
1 1 .0 
o-5 


13 


10.3 
1 1. 8 

79-3 
7.8 


n-3 


1 1. 9 


% 


% 
13.0 


3-2 
3-3 

8-5 

2.4 

25-1 
1.0 
1.2 


4-5 

4-2 


6.6 

5-2 

6.7 

5-8 
7-5 

7-8 

6.8 

1.8 

13-4 

2-3 

6-5 

2-3 

5-3 
10.7 
11 .0 
10.3 


10.9 
10.3 


'; 

10. o 
1 1. 4 


3-8 
•3 

7-9 
17.6 
32.0 
80.8 
78.9 
95  -o 


1.1 
1.2 
1-7 

1.0 

•5 

.2 

6.6 
•5 


% 


5-i 

54-i 
4-5 
2.4 


17-4 


76.1 
75-9 
7i-5 
76.3 
73-5 

76.3 
76.9 
17.4 
65.2 

"•3 

76.9 
23.8 


.8 

76.9 

1.7     70.9 

1.6     70.1 

2.0 

70.4 

i-7 

70.2 

1.4 

7-7 

% 

.8 
.6 


•5 
•5 

1.4 

•4 
2.9 

2-3 

4-7 


1.6 

•5 


APPENDIX 


58l 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued) 


Kind  of  Food  Material. 


£■0 


Edible  Portion. 


Available  Nutrients. 


Vegetable  Foods. 

Cereals,  etc. 
Wheat  flour: 

Family    and    straight 
grade 

High  grade 

Wheat  preparations: 

Breakfast  foods 

•     Macaroni 

Macaroni,  cooked 

Spaghetti 

Noodles 

Bread : 

Brown 

Corn  (johnnycake) .... 

Rye 

Graham 

Whole  wheat 

White  wheat 

Biscuit,  soda* 

Rolls 

Toasted  bread 

Crackers: 

Boston  (split) 

Milk,  cream 

Graham 

Oyster 

Soda 

Water 

Cakes,  cookies,  etc.: 

Bakers'  cake 

Coffee  cake 

Gingerbread 

Sponge  cake 

Drop  cake 

Molasses  cookies 

Sugar  cookies 

Ginger  snaps 

Wafers 

Doughnuts 

Pie,  pudding,  etc.: 

Pie,  apple 

Pie,  custard 

Pie,  squash 


'< 


% 

12.8 
12.4 

9.6 
10.3 
78.4 
10.6 
10.7 

43-6 
38.9 
35-7 
35-7 
38-4 
"35-3 
22.9 
29.2 
24.0 

7-5 
6.8 

5-4 

4.8 

5-9 
6.8 

3i-4 
21.3 
18.8 

15-3 
16.6 
6.2 
8-3 
6-3 
6.6 
18.3 

42.S 

62.4 
64.2 


% 


% 


% 


73-5 
73-6 

74.0 

73  -o 
15.6 

75-i 
74-3 

46.2 

45-2 
52.0 

5i-3 
49.1 

52.3 
5i-8 
55-8 

60.3 

69.9 
68.5 
72-5 
69-3 
71.8 
70.6 

55-8 
61.9 
62.1 
64-5 
59-2 

74  -o 
71 .6 
74-3 
73  -o 

52-1 

41.8 

25-7 
21.4 


% 


1.6 


i-3 

1.4 

1-3 

1.1 
2.2 
1.6 
1-4 

.6 


i-4 
.6 

i-7 
1.0 
2.0 
1.2 

•7 

1.4 


Calo- 
ries. 


1615 
1620 

1670 
1640 
405 
1640 
1640 

1035 
1 1 70 
1 1 60 
H85 
1125 

II9S 
1655 
1360 
1390 

1830 
1920 
1900 

I9°S 

1870 
1850 

1335 
1580 
1620 

1735 
1805 

1855 
1865 

1845 
1855 
1895 

1215 

795 
800 


*  Made  from  wheat  flour,  raised  with  baking  powder. 


58: 


SCIENCE    OF    NUTRITION 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued) 


Kind  of  Food  Material. 


as 

p5"° 


Edible  Portion. 


Available  Nutrients. 


Vegetable  Foods. 
Cereals,  etc. 
Pie,  pudding,  etc.: 

Pudding,  Indian  meal . 
Pudding,  rice  custard  . 
Pudding,  tapioca 

Sugars,  starches,  etc. 

Sugar,  granulated 

Sugar,  pulverized 

Sugar,  brown 

Sugar,  maple 

Molasses 

Maple  syrup 

Cornstarch 

Tapioca 

Sago 


% 


Vegetables. 

Asparagus,  fresh 

Asparagus,  cooked 

Beans,  Lima,  green 

Beans,  Lima,  dried.  .  .  . 
Beans,  string,  fresh .... 
Beans,  string,  cooked* . 
Beans,  white,  dried .... 

Beans,  baked 

Beets,  fresh 

Beets,  cooked* 

Beet  "greens,"  cooked*. 

Cabbage 

Carrots,  fresh 

Carrots,  evaporated. . . . 

Cauliflower 

Celery 

Sweet  corn,  green 

Cucumbers 

Egg  plant 

Lettuce 

Onions,  fresh 

Onions,  cooked* 

Parsnips 

Peas,  dried 

Peas,  green 


55  -o 

7.0 


i5-° 

20.0 


20.0 
61.0 
15.0 


i5-o 
10. o 


20.0 
45  -o 


% 
60.7 

59-4 

04-5 


1 1. 4 


% 
2-5 
2.1 
1 .0 


•7 
1 .0 
2.7 
6.7 
1 .0 

■5 
7-5 
2.8 
1 .0 
1.2 
1.2 

•7 
1.0 
6.9 

•7 

.6 

1.8 

•4 
.6 

•5 


7.6 
2.2 


% 
4-5 
3-2 
2.8 


1-3 
i-7 

5-3 
12.8 

i-7 
.6 
15-8 
4.8 
1 .2 
i-7 
i-7 
1.2 

•7 
5-8 
i-3 

.8 

2-3 
.6 

•9 

•9 

1.2 

•9 
1.2 

17-3 
5-2 


/o 
4-3 
4-i 
2.9 


% 
26.9 

3°-7 
28.2 


1 00.0 
100. o 
95 -o 
82.8 
70.0 
71.0 
90.0 
88.0 
78.1 


3-3 

2.1 
21.6 
65.6 

7 

1.9 

59-9 

19.6 
9.4 
7.2 
3 

5-5 
8.9 

76.9 
4-7 
3-2 

19.0 

3-o 
4-9 
2.9 
9.6 
4.8 

13-0 
62.5 
16.7 


% 
1.1 

•5 
.6 


*  With  butter,  etc.,  added. 


APPENDIX 


583 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued) 


Kind  of  Food  Material. 


53 


Edible  Portion. 


>  a 


Available  Nutrients. 


"3      •'°    Ml* 


Vegetable  Foods. 
Vegetables. 
Peas,  green,  cooked*. . . . 

Potatoes 

Potatoes,  cooked,  boiled. 
Potatoes,  mashed  and 

creamed 

Pumpkins 

Radishes 

Rhubarb 

Squash 

Spinach,  fresh 

Spinach,  cooked* 

Sweet  potatoes,  fresh. . . . 
Sweet  potatoes,  cooked*. 

Tomatoes 

Turnips 


% 


Vegetables  (canned). 

Asparagus 

Beans,  baked 

Beans,  string 

Beans,  Lima 

Sweet  corn 

Peas,  green 

Succotash 

Tomatoes 


50.0 
30.0 
40.0 
jjoT.o 


7o 
73  ' 
78 
75 

75 
93 
9i 
94 


30.0 


Fruits,  etc.  (fresh). 

Apples 

Apricots 

Bananas 

Blackberries 

Cherries 5.0 

Cranberries ...    |  88 

Currants j    ...      85 


25.0 

6.0 

35-° 


Figs. 

Grapes 

Huckleberries. 

Lemons 

Muskmelons.  . 

Oranges 

Pears 

Plums 


25.0 


1.6 

i-5 

2.7 

i-5 
2.0 
1.2 

i-7 

2.2 

2-4 

2.0 
1.2 
1.1 


% 
5-i 
i-7 
1 .9 


1 .0 

•4 

1 .1 
1.6 
1.6 

i-3 

2 .2 

•7 
1.0 


•3 

•9 

1 .0 

1 .0 

.8 

•3 
1 .2 
1.2 
1.1 

•5 


30.0 

50.0  89.5  1.1  .5 
27.0  86.9  1.4  .6 
10.0  I  84.4      1.7 

5-o 

*  With  butter,  etc.,  added. 


% 


% 


■9 
1.6 
1 .0 
1.2 


•5 

12.8 
12.2 

•5 

19.9 

. 

•9 

9.9 

•7 

i5-i 

•5 

8.9 
1 1. 6 

17.0 

•4 

17-3 

•5 

14.9 

.6 

7-7 
8.4 

.2 

IO-5 

•4 

12.7 

18.2 

Calo- 
ries. 
490 
370 
415 

475 
no 

130 
100 
205 
100 
235 
545 
885 
100 
175 


80 

555 
90 

335 
43° 
235 
425 
100 


260 
240 
400 

235 
320 
190 
230 
33° 
39° 
300 
180 
160 
210 
255 
345 


584 


SCIENCE    OF    NUTRITION 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued) 


Kind  of  Food  Material. 


Edible  Portion. 


Available  Nutrients. 


0  a 

•o « 

n-n 

j= 

O  >. 

.c 

< 

% 

% 

17. 1 

•5 

II.4 

•5 

6.8 

•5 

6.0 

.2 

59-6 

i-5 

56-5 

1.8 

70.3 

•7 

67.0 

3-« 

70.7 

1 .0 

67.0 

1.8 

68.7 

2.6 

66.1 

i-7 

15-7 

■3 

50.9 

•5 

"5 

•3 

19. 1 

•4 

49 -o 

•4 

Q.8 

.2 

16.2 

.2 

21.7 

•4 

15.6 

i-5 

3-2 

2.2 

37-9 

1.0 

25.1 

i-3 

11. 7 

1.8 

10.3 

1.6 

22.0 

i-5 

VEGETABLE   FOODS. 

Fruits,  etc.  {fresh). 

Prunes 

Raspberries,  black 

Strawberries 

Watermelons 


Fruits,  etc.  {dried). 

Apples 

Apricots 

Citron 

Currants 

Dates 

Figs. 

Raisins 

Prunes 


Fruits,  etc.  {canned). 

Apricots 

Blackberries 

Blueberries 

Cherries 

Crab-apples 

Peaches 

Pears 

Strawberries  (stewed) .  .  . 


Nuts. 

Almonds 

Butternuts 

Chestnuts  (fresh). 

Cocoanuts 

Filberts 

Hickorynuts 

Peanuts 


/o 
6.0 


5-° 

60.0 


10.0 

150 


45 -o 
86.0 
16.0 
49  -o 
52.0 
62.0 
25.0 


% 

% 

79.6 
84.1 

2.1 
i-7 

90.4 

1 .0 

92.4 

•9 

28.1 

7-5 

29.4 

7-7 

19.0 

17.2 

H-3 

8.6 

15-4 
18.8 

8.8 
8.7 

14.6 

9.1 

22.3 

8-3 

81.4 

1.9 

40.0 
85.6 

6.1 
1.6 

77.2 

2-3 

42.4 
88.1 

5-7 
i-3 

81. 1 
74.8 

1.9 

2.6 

4.8 

10.9 

4 

4 

1 1. 4 

45 

0 

5-9 

14 

1 

9.2 

3 

7 

10.7 

3 

7 

10.6 

9 

2 

10.7 

% 

•7 

1.4 

.8 

■3 


i-3 

3-7 

•4 

1.9 

1.6 

3-4 
2.0 
1.6 


17.8 

23-7 
5-3 
4.8 

13-3 
i3-i 
21.9 


% 


2.0 

•9 

i-3 

i-5 

2-5 

■3 
3-o 


Calo- 
ries. 

325 
270 
160 
125 


1 190 
1 130 
I340 
1315 
1415 
1290 
1410 
1230 


295 
1015 
240 
365 
985 
190 
310 
400 


2685 
2805 
990 
2460 
2930 
2980 
2255 


For  greater  detail  see  The  Chemical  Composition  of 
American  Food  Materials,  by  Atwater  and  Bryant,  Bulletin 
28  (Revised),  U.  S.  Dept.  of  Agriculture,  Washington,  1902. 


INDEX 


Abderhalden 

alcohol  and  alcoholism,  358 
amino-acids  in  blood  serum,  82 
composition  of  proteins,  77 
importance  of  high  protein  dietary, 

.343 
nitrogen  equilibrium 

with  amino-acids,  159 
with  ammonium  salts,  284 
with  urea,  284 
pyrimidin  bases  and  purins,  528 
value  of  proteins  in  nutrition,  157 
Abderhalden  and  Bergell 

amino-acids  in  urine  in  phosphorus 
poisoning,  492 
Abderhalden,  Bergell,  and   Doerping- 
haus 
composition  of  cells  at  death, 
102 
Abderhalden  and  Bloch 

alcaptonuria,  163 
Abderhalden  and  Einbech 

fate  of  histidin  in  body,  205 
Abderhalden  and  Kautzsch 

pyrrolidon   carboxylic   acid   from 
glutamic  acid,  202 
Abderhalden  and  Lampe 

tributyrin  splitting  by  blood,  96 
Abderhalden  and  Langstein 

amino-acids  in  milk,  400 
Abderhalden,  London,  and  Pincussohn 
kynurenic    acid    from    trypto- 
phan, 81 
Abderhalden,   London,   and    Schitten- 
helm 
uric  acid  elimination  after  Eck 
fistula,  536 
Abderhalden  and  Rona 

nitrogen  equilibrium   with  cleav- 
age products  of  casein,  158,  159 
Abderhalden  and  Samuely 

protein  construction  in  the  body, 
160 
Abderhalden  and  Strauss 

elimination  of  glycocoll,  186 
Abel,  82 


Abel,  Rowntree,  and  Turner,  81 
Absorption 

of  amino-acids  by  blood,  79 
of  animal  and  vegetable  foods,  54 
"Accessory  factors"  of  diet,  363 
"Accessory  food-stuffs,"  363 
"Accessory  food  substances" 

influence  upon  growth,  369 
necessity  of,  362,  363 
Acclimatization 

effect  of,  in  mountain  climbing,  427, 

431 
process  of,  at  high  altitudes,  435, 

436 
tension  of  alveolar  gases  in,  table, 

437 
Acetaldehyd 

acetic  acid  from,  192 
alcohol  from,  192 

as    cleavage    product    of    carbohy- 
drate, 267,  268 
Acetic  acid  from  acetaldehyd,  192 
Aceto-acetic   acid   from   B-oxybutyric 

acid,  466 
Aceton  bodies 

in  blood,  table,  466 
from  fat  in  organism,  250 
from  homogentisic  acid,  197 
from  muconic  acid,  197 
partition   of,   in   severe   diabetes, 

466 
source  of,  in  diabetes,  464,  465, 

466 
from  valin,  194,  195 
Acetonuria    in    starvation,    table,   93, 

94 
Acetylation  in  organism,  199 
Acid 

formation    in    body,     quantity    of, 
217 
indexed  by  urinary  ammonia,  214, 
221 
ingestion  and  urinary  ammonia,  219; 
table,  220 
Acid  phosphate,  retention  of,  498 
Acidity,  urine  titratible,  217 

585 


586 


INDEX 


Acidosis 

as  cause  of  increased  metabolism  in 
diabetes,  475 

effect   of   carbohydrate   upon,    271, 
272 

effect  of,  on  blood,  467 

in  fasting,  93 

hydrogen-ion  concentration  of  blood 
in,  table,  468 

in  infants,  497 

treatment  of,  table,  498 

influence  of,  upon  storage  of  glyco- 
gen, 447 

in  obesity  during  fasting,  table,  94 

persistence  of,  after  mountain  climb- 
ing, table,  434 

production  of,  467 

of  renal  origin,  496 
Acids 

action  of,  upon  mutarotation,  261 

effect  of,  upon  glycogen  discharge  by 
the  liver,  447 

influence  of,  in  asphyxial  glycosuria, 

447 
Ackermann,  201 
Ackroyd,  538 

Acromegaly,  basal  metabolism  in,  439 
Activity,  influence  of,  on  basal  metab- 
olism in  typhoid  fever,  519 
Adenase 

action  of,  533 

occurrence  of,  533 
Adenin 

fate  of,  532 

structure  of,  527 
Adenosin 

fate  of,  when  injected,  539,  548 

inosin  from,  530,  531 
Adler,  490 

Adolescence,   food  consumption   dur- 
ing, 559 
Adrenalin,  influence  of,  on  sugar  for- 
mation, 458,  459,  460 
Agar-agar 

effect  of,  upon  heat  production,  232 

nutritive  value  of,  54 
Age,  128,  407,  559 
Air 

alveolar,    carbon    dioxid    of,    after 
moderate  exercise,  322 

expired,  early  observations  of,  21,  22 
Alanin 

glucose  from,  194 

glycogen  from,  191 

from  glycogen,  194 

lactic  acid  from,  191 

oxidative  deamination  of,  178,  179 

from  pyruvic  acid,  104 

specific  dynamic  action  of,  240,  241 


/^-Alanin,  from  aspartic  acid,  201 
d-Alanin 

fate  of,  191 

glucose  from,  191 

occurrence  of,  191 
d-1-Alanin,  d-glucose  from,  193 
1-Alanin,  glucose  from,  191 
Albarran,  165 
Albertoni  and  Rossi,  342 
Albu  and  Neuberg,  358 
Albumen,  in  starvation  urine,  92 
Albumoses,  in  urine  during  fever,  523 
Alcaptonuria,  178 

effect  of  water  drinking  upon  urine 
from,  163 

origin  of  homogentisic  acid  in,  195, 
196 
Alcohol 

from  acetaldehyd,  192 

in  animal  economy,  355;  table,  356 

in  blood,  356,  357 

from   carbohydrate   in   metabolism, 
how  prevented,  268 

in  fatigue,  325 

when  indicated,  358 

in  milk,  397 

influence  of,  on  metabolism,  table, 
350 

and  obesity,  356 

oxidation  of,  in  body,  356,  357 

respiratory  quotient  after  ingestion 
of,  357 

and  uric  acid,  31,  545 

use   of,   in   treatment    of    diabetes, 
480 
Alcohol  check,  definition  of,  56 
Alcoholics,  retention  of  purins  by,  545 
"Aldehyd  mutase,"  192 
Alkali  therapy 

in  depancreatized  dog,  485 
in  diabetes,  484 
Alkaloids,    food,    effect    of,    on    purin 

bases  in  urine,  532 
Alkalosis,  444 
Allantoin,  335,  338 
Allard,  453,  457 
Allen 

fasting  in  diabetes,  480 

islands  of  Langerhans  in  diabetes, 
488 
Allen  and  Du  Bois 

energy  production  in  diabetes,  474, 

475 
non-protein    respiratory   quotient 

in  severe  diabetes,  471 
Almagia,  546 
Almond  oil,  influence  of,  on  growth, 

369 
Alsberg  and  Folin,  199 


INDEX 


587 


Altitude    and    atmospheric    pressure, 

table,  426 
Altitudes 

acclimatization  process  at  high,  435, 

430. 
capacity  for  work  at  high,  430,  431 
carbohydrates  in  diet,  value  of,  at 

high,  433 
Cheyne-Stokes  respiration  in   high, 

43°. 
fatty  infiltration  at  high,  423 
hemoglobin  in  blood  at  high,  435,  436 
lactic  acid  in  blood  at  high,  433 
metabolism  at  high,  418,  429,  431, 
437,  438 
how  studied,  426 
retention 

of  iron  at  high,  435 
of  nitrogen  at  high,  435 
of  potassium  at  high,  435 
ventilation    of    lungs    at    various, 
table,  431 
Alveolar  air,  219,  322,  434,  468 
Am  bard,  165 

Ambard's  coefficient,  166 
Amberg  and  Jones,  530 
Amino-acids 
absorption 
by  blood,  79 
of,  and  metabolism,  245 
aromatic,   fate   of,   in  alcaptonuria, 

behavior  of,  in  bod}',  how  studied, 
176 

in  blood,  81,  82 

after  feeding  meat.  80 

after  glycocoll  absorption,  So 

and  tissues,  80 

from  casein,  specific  dynamic  action 
of,  239 

chemical  stimulus  by,  245,  301 

in  diabetic 
blood,  464 
urine,  464 

digestion,  rapidity  of,  242,  243 

fate  of.  184 

glucose  from,  184,  242 

guanidin  nucleus  in,  204 

laws  of  fate  of,  in  organism,  177 

in  liver  after  phosphorus  poisoning, 
492 

metabolism  after,  chart,  241 

in  milk,  400 

production  of,  in  tissues  in  fasting,  82 

and  protein  metabolism,  78,  79 

pure   mixed,    and   nitrogen   equilib- 
rium, 159,  160 

rapidity  of  metabolism  of,  242 

retention  in  organs.  81 


Amino-acids 

specific  dynamic  action  of,  241,  243 
story  of  metabolism  of,  184 
synthesis  of, "in  organism,  284 
urea  from,  79,  176 

in  urine  after  phosphorus  poisoning, 
.492 

in  various  proteins,  table  of,  77 
Ammonia 

absence  in  expired  air,  22 

excretion  in  fasting,  92,  93 

as  index  of  acid  formation,  214,  221 

influence  of  fat  upon,  222 

after  ingestion  of  acid  phosphates, 

222 
production,  function  of,  222 
after  sodium  bicarbonate  ingestion, 

222 
urinary 

after   acid   ingestion,    table,    219, 

220 
and  food  intoxication  of  infants, 
220 
Ammonium     acetate,     as     sparer     of 
endogenous  protein  metabolism,  283 
Ammonium  carbonate,  urea  from,  222 
Ammonium  chlorid,  as   sparer  of  en- 
dogenous protein  metabolism,  284 
Ammonium    citrate,   as   sparer  of  en- 
dogenous protein  metabolism,  283 
Anabolism,  definition  of,  20 
Anaphylaxis,  161 
Andersen,  A.  C,  see  Henriques,  161, 

284 
Andersson,  J.  A.,  and  Bergman,  440 
Andersson,  O.,  443 
Anemia 
artificial 

blood  gases  in,  421,  422 
heat  production  of,  422 
hemoglobin  in,  423 
protein  metabolism  in,  421 
blood  gases  in,  425 
composition  of  hemoglobin  in,  425 
glucose  in  urine  in,  421,  422 
hemoglobin  in,  424 
lactic  acid  in  urine  in,  421,  422 
metabolism  in.  chapter,  418 

calorimetric    observations,    table, 
4-24 
pernicious,  metabolism  in,  424 
Apnea,  oxygen  absorption  in,  32 
Appetite,  as  expression  of  hunger,  107 
Arabinose,  fate  of,  in  body,  487 
Araki 
glycosuria  after  exposure  to  cold,  440 
lactic  acid 

in  phosphorus  poisoning,  493 
in  urine  after  blood-letting,  422 


58* 


INDEX 


Area  (surface),  41,  118,  124 

of   body   measured   and   calculated 
and  by  linear  formula,  table,  125 

of  cattle  and  nitrogen  content,  130 

and  heat  production  in  various  rest- 
ing animals,  table,  119 

of  infants,  409 

interpretation  of  law  of,  120,  121 

law  of,  41,  119,  483 

linear  formula  for,  125 

Lissauer's  formula,  406 

of  man,  chart  for  determining,  126 

Meeh's  formula,  118 

and  metabolism,  122 

of  yeast,  121,  122 
Arginase 

action  of 

on  creatin,  205 
on  guanido-acetic  acid,  205 
Arginin 

fate  of,  203 

glucose  from,  203,  204 

occurrence,  203 
d-Arginin 

ornithin  from,  204 

urea  from,  204 
Armand-Delille,  Mayer,  Schaffer,  and 

Terroine,  285 
Armsby  and  Fries,  51 
Aron,  415 
Arteaga,  455 
Arthritis 

differential  diagnosis  from  gout,  547 

tubercular,  relations  in,  chart,  524 
Arthritis  deformans 

non-protein  nitrogen  in  blood  in, 

547 
Artichokes,  nutritive  value  of,  54 
Ascaris,  fat  from  carbohydrate  by,  305 
Ash 

balance  of,  in  fasting,  table,  98 

of  human  muscle,  98 

importance  of 

acid  or  base  forming  potency  of, 

in  different  foods,  361 
in  dietary,  358 

of  milk,  absorption  of,  table,  398 

of  ordinary  dietaries,  table,  359 

of  various  edible  foods,  table,  360 
Asher,  see  Rosenfeld,  452 
Aspartic  acid 

J-alanin  from,  201 

fate  of,  200 

glucose  from,  200,  201 

occurrence  of,  200 

primary  cleavage  products  of,  201 

pyruvic  acid  from,  201 
Asphyxia,  lactic  acid  in  urine  during, 

266 


Assymetry 

of  carbon  atom,  how  abolished,  266 

loss  of,  191,  192 
Atmosphere 

constancy  of  composition  of,  427 
Atmospheric  pressure 

and  altitudes,  table,  426 

diminished,    and    protein    metabol- 
ism, 427 

and  metabolism,  428 

and  respiratory  metabolism,  428 
Atropin 

influence  of,  upon  basal  metabolism, 

553 
Atwater 

dietaries  for  farmers,  348 
protein  in  diet  of  laborer,  335 
Atwater  and  Benedict 

accuracy  of  calorimeter,  56 
alcohol  in  humna  economy,  355 
metabolism  in  severe  work,  320 
sugar    from  fat    in    metabolism, 

3i9 
Atwater  and  Rosa,  calorimeter  of,  56 
Aub  and  Du  Bois,  127 
Aub,  see  Means,  425,  554 
"Auspumpung,"  definition  of,  145 
Austin  and  Ringer,  451 
Austin,  see  Pepper,  167 
Austrian,  see  Jones,  533,  534 
Autolysis  in  phosphorus  poisoning,  492 
Auto-toxemia,  relief  of,  in  fasting,  by 

meat  ingestion,  104 
Avoirdupois  and  metric  weights,  com- 
parison, 574 


BABAK,  138 

Bachl,  22 

Bacillus,  tubercle,  protein  synthesis  by, 

285 
Bacteria 

action  upon  phenyl-alanin,  179 

and  fecal  nitrogen,  55 

in  feces,  54 

formation  of 

cadaverin  from  lysin,  203 

indol  and  skatol  from  tryptophan, 

206,  207 
putresin  from  ornithin,  204 

nitrogen  from,  in  rat  feces,  55 
Baehr,  see  Epstein,  448 
Baer  and  Blum,  195 
Baer,  see  Parnas,  190,  195 
Bailey  and  Murlin,  404,  406 
Bailey,  see  Murlin,  214,  384 
Baker,  see  Gettler,  495 
Baldes,  see  Embden,  195,  265 
Baljarski,  see  London,  210 


INDEX 


589 


Balloon  ascension 

experiences  of  Tissandier  and  Sivel, 
426 

metabolism  during,  428 
Bananas 

as  exclusive  food,  355 

protein  utilization  of,  355 
Bang,  528 
Barcroft,  ^22 
Barcroft  and  King,  433 
Barley  water,  use  of,  in  milk,  400 
Barr,  see  Coleman,  509 
Barrenscheen,  190 
Barringer  and  Barringer,  165 
Bartmann,  248 
Basal    metabolism,    see    Metabolism, 

basal. 
Batelli  and  Stern,  192 
Baths 

cold 

effect  of,  506 

and  metabolism,  table,  143,  144 

hot 

and  cold,  and  metabolism,  table, 

.I45 
effect  upon  metabolism,  500 

Baudouin,  see  Gilbert,  291 

Bauer,  S4,  421 

Baumgarten  and  Grund,  483 

Beans,  string,  value  of,  as  food,  54 

Beaute,  Victor,  urinary  analysis  during 
fasting,  table,  92 

Becker  and  Hamalainen,  348 

Beebe,  31,  544 

Beef,  Liebig's  Extract,  food  value  of, 
352 

Beef  fat,  influence  of,  on  growth,  369 

Beer,  absorption  of,  355 

Beger,  see  Morgan,  303 

Begun,  Hermann,  and  Muenzer,  220 

Bellevue    Hospital,    respiration    calor- 
imeter in,  description  of,  63 

von  Benczur  and  Fuchs,  550 

Bendix,  see  Schittenhelm,  534 

Benedict,  F.  G. 

body  temperature  in  men,  113 
cause  of  specific  dynamic  action  of 

carbohydrates,  295 
cretin  in  urine  of  fasting  man,  212 
cutaneous  excretion,  22 
feces  in  fasting,  51 
heat  production  during  sleep,  122 
influence    of    glycogen    on    protein 

metabolism  in  fasting,  72 
metabolism 

in  fasting,  88,  97 
and  Newton's  law,  122 
in  the  early  days  of  starvation,  90 
N  :  S  ratio  in  starvation,  92 


Benedict  and  Carpenter 

description  of  Atwater-Rosa  calor- 
imeter, 63 
loss  of  water  from  lungs  and  skin, 

131 
Benedict  and  Cathcart 

increase  in  basal  metabolism  after 

severe  work,  322 
metabolism  during  bicycle  riding, 
320 
Benedict,  Cushny,  Meltzer,  and  Lusk 

use  of  alcohol  in  medicine,  358 
Benedict  and  Emmes 
"Darmarbeit,"  2^2 
heat  production  of  women,  383 
Benedict,  Emmes,  Roth,  and  Smith 

normal  controls,  127 
Benedict  and  Joslin 

cause  of  specific  dynamic  action 

of  carbohydrates,  295 
energy  production  in  diabetes,  474 
Benedict  and  Milner 

C  :  N  ratio  in  man  on  mixed  diet, 

38 
water  loss  in  body  on  change  of 

diet,  272 
Benedict  and  Murschhauser 

economy  in  walking  and  running, 

329 
energy  summation  from  food  and 

work  during  walking,  312 
metabolism  of  bicycle  rider,  331 
Benedict  and  Pratt,  "Darmarbeit,"  231 
Benedict  and  Slack,  rectal  temperature 

as  index  of  body  temperature,  133 
Benedict  and  Talbot 

metabolism  of  infants,  406,  407 
oxidative  processes  in  metabolism, 
62 
Benedict,  F.  G.,  see  Atwater,  56,  319, 
320, 355 
see  Carpenter,  425 
Benedict,  S.  R. 
uric  acid 

and     allantoin     in     Dalmatian 

hound,  537 
elimination    after   ingestion    of 

caffein,  532 
in  fowl's  blood,  543 
in  ox  blood  corpuscles,  549 
Benedict  and  Lewis 

D  :  N  ratio  in  phlorhizinized  man, 

455 
Benedict  and  Osterberg 

creatinin  elimination  and  cellular 
destruction,  212 
Benedict,  S.  R.,  see  Guion,  452 
Benedikt,  H.,  and  Torok,  B. 

use  of  alcohol  in  diabetes,  480 


59Q 


INDEX 


Benjamin,  524 
Benzoic  acid 

from  cinnamic  acid,  183 

from  phenyl  -  fi  -  keto  -  propionic 
acid,  183 

when  eliminated,  185 
Benzol,  muconic  acid  from,  197 
Berg,  Du  Bois-Reymond,  and  L.  Zuntz, 

333 
Bergell,  see  Abderhalden,  102,  492 
Berger,  174 

Bergman,  see  Andersson,  J.  A.,  440 
Beri-beri,  362 

and  rice  bran,  367 
Bernard,  Claude,  132,  445 
Bernstein,    Balaffio,    and   Westenrijk, 

458 
Bertram,  358 
Bicycle     riding,     metabolism     during, 

table,  320,  321 
Bidder  and  Schmidt 

calculation  of  heat  of  metabolism, 

36 
"intermediary"  metabolism,  171 

respiratory  exchange  after  meat, 

223 
urinary  nitrogen  as  index  of  pro- 
tein destruction,  20 
Bile 

glucose  in,  after  phlorhizin,  451 
in  starvation,  105 
Billstrom,  see  Johansson,  289 
Biochemical  interconversions,  scheme 

of,  267 
Birds 

uric  acid  production  in,  541 
urine,  composition  of,  table,  541 
Birth,  respiratory  quotient  at  time  of, 

404 
Bischoff  and  Voit 

early  methods  of  metabolism  cal- 
culation, 24 
feces   production   after   meat   in- 
gestion, 48 
gelatin  in  metabolism,  156 
heat  value  of  metabolism,  early 

calculations  of,  36 
loss  of  water  in  body  with  change 

of  diet,  272 
urea  excretion  in  diet,  153 
Blackfan,  see  Jackson,  549 
Bladder,  infection  of,  and  ammonia  in 

urine,  214 
Blatherwick,  217,  361 
see  Janney,  456 
see  Underhill,  444 
Blauberg,  308 
Bleibtreu,  Max,  306 
Bloch,  see  Abderhalden,  163 


Blood 

Abel's  diffusate,  81 

absorption  of  amino-acids  by,  79 

aceton  bodies  in,  table,  466,  468 

air    exchange    with,    how    accom- 
plished, 418 

alcohol  in,  356,  357 

alkali  reserve  of,  221 

alkalinity    of,    and    strychnin    con- 
vulsions, 493 

amino-acid 

content  after  absorption  of  gly- 

cocoll,  80 
nitrogen  in,  after  plasmapharesis, 

.  83 
amino-acids  in,  80,  82 

after  taking  meat,  80 
ammonia  in,  after  Eck  fistula,  22 
arterial 

and  alveolar   carbon   dioxid  ten- 
sion of,  218 

carbon    dioxid    tension    of,    after 
hard  exercise,  322 
carbon  dioxid  in,  in  liver  perfusion, 

296 
chicken,  uric  acid  in,  543 
corpuscles  in  fasting,  106 
diabetic,  amino-acids  in,  464 
dilution  of,  after  glucose  ingestion, 

292 
early  views  of  oxidation  within,  19 
effect  of 

acidosis  upon,  467 

plasmapharesis  upon  composition 
of,  table,  83 
fat 

in  diabetes,  490 

in,  during  fasting,  107 

after  fat  ingestion,  251 

during  starvation,  249 
first  isolation  of  amino-acids  from,  81 
flow,    activity   of,   and   body   tem- 
perature, 134 
gaseous  exchange  in,  table,  418 
gases  in 

anemia,  425 

artificial  anemia,  421,  422 
glycolysis,  264 
hemoglobin 

at  high  altitudes,  435,  436 

in  anemia,  424 

in  artificial  anemia,  423 
hydrogen-ion     concentration,     214, 

215 
in  acidosis,  468,  498 
influence 

of  moderate  exercise  on,  322 

of  neurogenic  fever  on,  504 

and  respiration,  218 


INDEX 


591 


Blood 

lactic  acid  in 

at  high  altitudes,  433 

after  moderate  exercise,  explana- 
tion of,  2,22,  323 
letting 

metabolism  after,  421 

nitrogen  in  urine  after,  84 
non-protein  nitrogen  in 

in  arthritis  deformans,  547 
in  gout,  547 
normal 

alcohol  in,  356 

d-lactic  acid  in,  263 

/i-oxybutyric  acid  in,  250 

uric  acid  in,  547 
ox,  uric  acid  in,  543 
oxygen  absorbing  capacity  of,   and 

decreased  oxygen  tension,  432 
oxyhemoglobin  and  carbon  monoxid 

poisoning,  434 
plasma-nitrogen,    in   fasting,    table, 

106 
plethora,     artificial     effect    of,     on 

metabolism,  422 
protein  and  food  protein,  160 
proteins,   effect  of  ingested  gliadin 

upon,  160 
reaction 

effect  of  change  of,  219 

how  maintained,  208,  214,  216,-217 

of,  in  severe  diabetes,  table,  221 
sodium   chlorid   in,   in   pneumonia, 

522,  523 
splitting  of  tributyrin  in,  bv  fasting, 

96 
sugar 

in  anemia,  421 

colloidal,  451,  462 

diffusibility  of,  452 

and   environmental   temperature, 

after  glucose  ingestion,  291 
transfusion,  effect  on  diabetes,  484 
urea  in 

in  nephritis,  495 
after  plasmapheresis,  83 
uric  acid  combined  in,  543 
uric  acid  in 

in  gout,  547 

discovery  of,  544 
after  ingestion  of  purins,  549 
in  lead  poisoning,  547 
in  nephritis,  547 
Bloor,  250 
Blum,  L. 

fate  of  cystin  in  bod}',  198 
oatmeal  cure  in  diabetes,  483 
see  Baer,  195 


Blum,  P. 

glycogen    in    liver    after    strychnin 
convulsions,  447 
Boarding  school,  boys' 

annual  supplies  for  table,  558 
cost  of  food  at,  558 
distribution  of  food  calories  in, 

560 
food  supply  per  meal,  table,  558 
nutritional  conditions  at,  table, 

559 
Body,  human,  efficiency  of,  312,  321 
Body  temperature 

high,  and  dissociation  of  oxyhem- 
oglobin, 433 
in  mountain  sickness,  433 
Body  weight 

and   heat   production  in  infants, 

chart,  408 
loss  of,  in  exclusive  protein  me- 
tabolism, 102 
Boehm  and  Hoffmann,  449 
Bolaffio,  see  Bernstein,  458 
Boldireff,  70 

Bommes,  see  Thannhauser,  539,  548 
Bookbinders,  energy  requirement,  349 
Boothby,  127 
Bornstein 

protein  retention 
on  low  diet,  154 
during  work,  317 
Bornstein  and  Mueller,  434 

death  after  hemoglobin  reduction, 
434 
Bostock,  Gertrude,  176 
Bosworth,  400 
Bowen,  see  Higley,  325 
Boycott  and  Haldane,  433 
Boys 

food  consumed  by,  559 
metabolism 
basal,  559 

of,  fat  and  thin,  129 
Boys'  boarding    school,  see    Boarding 

school. 
Brasch,  488 

Brasch  and  Neuberg,  462 
Bread 
imperfectly  cooked,  feces  from,  52 
influence  of,  upon  feces,  49 
nitrogen    equilibrium    on    exclusive 

diet  of,  354 
protein,  utilization  of,  341 
Breithaupt,  feces  of,  in  fasting,  51 
Brener  and  von  Seiller,  438 
Brezina,  see  Toegel,  290,  357 
Brezina  and  Kolmer 

respiratory  quotients  during  work, 
323 


59- 


INDEX 


Brezina  and  Reichel 

effect  of  gradient  on  metabolism 
and  walking  and  carrying  dif- 
ferent loads,  330 
influence  of  velocity  and  load  in 
walking  on  energy  required  for 
work,  328,  329 
Bright's  disease 

effect    of    phlorhizin    injections   in, 
45° 
Broden  and  Wolpert,  313 
Brown,  see  Fletcher,  264 

see  Mendel,  543 
Brugsch,  93 
Brunton,  Lauder,  534 
de  Bruyn,  Lobrey,  and  van  Eckstein, 

260 
Buergi,  332,  352 
Bunge 

ash  of  dogs'  milk,  397 

growth  and  percentage  composition 

of  milk,  397 
rapidity   of   growth   and   longevity, 
416 
Burckhardt,  106 
Burian,   source  of  endogenous  purin, 

54i 
Burian  and  Schur 

endogenous  uric  acid  elimination, 

539 
purin  content  of  various  tissues, 

54i 

Burton-Opitz,  134 

Butter-fat,  influence  on  growth,  369 

Butterfield,  425 

Butyric  acid 

from  glutamic  acid,  462 
/3-oxybutryic  acid  from,  465 


Cabbage,  value  of,  54 
Cadaverin,  from  lysin,  203 
CarTein 

fate  of,  532 

influence  of,  upon  basal  metabolism, 

553,  554 
uric  acid  in  urine  from,  532 
Cahn-Bronner,  276 
Calcium 

absorption  of,  in  growth,  412 
effect  of,  after  parathyroidectomy, 

444 
equilibrium,  358 
excretion  in  starvation,  92 
hunger,  definition  of,  69 
influence  of,  upon  growth,  374 
oxid 

daily  requirement  of,  358,  359 

in  diet  of  Finns,  359 


Calculi,  urinary,  discovery  of  uric  acid 
in,  526 

Calliphora,  production  of  fat  from  pro- 
tein by,  230 

Calorimeter 
of  Atwater-Rosa,  44,  56 
in  Bellevue  Hospital,  description  of, 

63 
of  Rubner,  43 
Calorimetry 
agreement  of  direct  and  indirect,  63 
direct  and  indirect,  correspondence 

between,  in  infants,  table,  405 
indirect 

example  of  calculation,  62 

method  of  calculation  when  quo- 
tient is  above  unity,  307 
in  typhoid  fever,  accuracy  of,  table, 

5i7 
Camerer,  398,  412 
Camerer,  W.,  Jr.,  403 
Camphor 

elimination  of,  in  urine,  486 
influence  of,  upon  basal  metabolism, 

553 
Cane  sugar,  see  Sucrose. 
Cannizzaro  reaction,  192,  266 
Cannon,  Stohl,  and  Wright,  449 
Cannon  and  Washburn,  70 
Carbohydrate 
acetaldehyd    as    cleavage    product 

from,  267,  268 
and  alcohol,  dynamic  action  of,  357 
alcohol  from,   in   metabolism,   how 

prevented,  268 
conversion  of,  into  fat,  304 
and  creatin  excretion,  212,  213 
diet  and  muscle  creatin,  213 
digestibility  of,  52 
economy  of,  288 
effect  upon  acidosis,  271,  272 
energy  from,  in  nutrition,  258 
and  fat 

in     metabolism,     calculation     of, 

table,  61 
relative  value  of,  for  mechanical 
work,  318,  319,  324 
fat  from 

reaction,  268,  306 
respirator}-  quotient  of,  306 
function  of,  in  hepatic  disease,  493 
glycogen  distribution  after  feeding 

of,  259 
heat  of  combustion  of,  42 
ingestion,  297,  298 
intermediary  metabolism,  258 
metabolism,  294 

acid  production  in,  296,  299 
dynamic  aspects  of,  302 


INDEX 


593 


Carbohydrate 

and  nitrogen  equilibrium,  277 

nutritional  heat  of,  42 

partial  replacement  of,  by  fat,  and 

protein  metabolism,  270 
plethora,  302 
protein-sparing,    property    of,    273, 

274 
and  protein 

retention,  table,  269,  270 
reduction  of,  285,  286,  501,  516 
respiratory 

metabolism  of,  289 
quotient  of,  29,  58 
specific  dynamic  action,  237 

cause  of,  295 
tolerance  in  affections  of  the  hypoph- 
ysis, 439 
value  of,  in  diet  at  high  altitudes,  433 
Carbon 

in  excreta,  Rubner's  experiment,  39 
excretionary,  as  index  of  fat  metab- 
olism, 40 
non-protein,  definition  of,  57 
retention    after    excessive    protein 
feeding,  223,  226 
Carbon  atom 

asymmetry  of,  how  abolished,  266 
Carbon  dioxid 

alveolar  tension,  219 
and  acid  urine,  218 
and  arterial  blood,  218 
of,  at  different  levels,  table, 

432 
of,  and  respiratory  center,  217 
arterial  blood  tension  after  hard 

exercise,  322 
bell-jar  experiments  of  Regnault 

and  Reiset  on  excretion  of,  23 
in  blood,  296 
cleavage 

followed  by  reduction,  180 
in  amino-acid  metabolism,  179 
combining  power  in  blood,  221 
elimination 

and  diurnal  temperature  varia- 
tion, curve,  in 
in  fasting,  86 
in  muscular  rest,  curve,  86, 

112 
during  work,  109 
after  fructose  ingestion,  289,  294 
in  frog  at  various  temperatures, 

curve,  114 
in    guinea-pig    at    various    en- 
vironmental      temperatures, 
table,  135 
during  mechanical  work,  325 
Carbon  monoxid,  "diabetes,"  462 

38 


Carboxylase,  action  of,  267 
Carcinoma 
increased  metabolism  in,  512 
toxic  destruction  of  protein  in,  512 
Cardiac  disease 

effect  of  digitalis  upon  basal  met- 
abolism in,  554 
heat  production  in,  497 
metabolism  in,  chapter,  495 
Cardiorenal  disease,  heat  production 

in,  497 
Carlson,  70 

Carlson,  Orr,  and  Jones,  453 
Carpenter,    energy    requirement    for 

typewriting,  349 
Carpenter  and  Benedict,  metabolism  of 
man  in  whom  left  lung  was  removed, 

425 
Carpenter    and    Murlin,    metabolism 

during  pregnancy,  382 
Carpenter,   see    Benedict,   F.    G.,   63, 

131 
Carpenters,    energy   requirements   ot, 

349 

Cartilage,  retention  of  urates  by,  547 

Casein 
comparative  value  of,  in  growth,  376 
glucose  derivable  from,  457 
influence  of,  upon  growth,  370 
specific  dynamic  action  of,  239 
amino-acids  from,  239 

Caspari  and  Loewy,  433 

Caspari,  see  Zuntz,  330,  435 

Castration,  influence  of,  upon  metab- 
olism, 438 

Catabolism,  definition  of,  20 

Cathartics,  effect  upon  heat  produc- 
tion, 232 

Cathcart 
creatin  in  urine  during  fasting,  212 
protein  sparing  by  starch  and  cream, 

273 

urine  in  fasting,  93 
Cathcart,  see  Benedict,  F.  G.,  320,  322 
Cathcart  and   Green,  deposit  protein 

after  feeding  egg  albumin,  169 
Cauliflower,  value  of,  as  food,  54 
Cecil,  459 
Cells 

mechanisms  for  food  influences,  303 

optimum  nutritive  condition,  287 
Cereals,  digestibility  of,  52 
Cetti,    metabolism   of,   in   starvation, 

table,  S7 
Chase,  see  Fine,  549 
Check 

alcohol,  definition  of,  56 

electric,  definition  of,  56 
Cheese,  ripening  of,  fat  during,  490 


594 


INDEX 


"Chemical  regulation,"  233.   See  Tem- 
perature. 
during  mechanical  work,  313 
Chemical    stimulus   and   amino-acids, 

245 
Chicken-pox,  urine  in,  524 
Childbirth,  protein  metabolism  before 

and  after,  table,  388 
Children,  see  Infants. 

energy  metabolism  of,  407 

growth  of,  in  relation  to  milk  in- 
gested, 410 

heat  production  and  age  of,  407 

mineral  metabolism  of  growing,  417 

"summer  troubles"  and  climate,  148 
Childs'   restaurants,   caloric   value   of 

food  sold  at,  table,  563-569 
Chill,  effect  of,  in  fever,  511,  512 
Chittenden 

bodily  vigor  and  protein  ingestion, 

337 
diet  and  uric  acid  elimination,  540 
dietary  for  soldiers,  345,  346 
mental    condition   and    protein    in- 
gestion, 339 
nitrogen  equilibrium  on  low  protein 

diet,  279 
physical  power  and  protein  inges- 
tion, 318 
Chloral,  elimination  of,  in  urine,  486 
Chlorophyll,  from  pyrrolidin  carboxylic 

acid,  203 
Chlorosis 
and  ovarian  insufficiency,  438 
metabolism  in,  424 
Cinnamic  acid 

benzoic  acid  from,  183 
phenyl-/3-oxy-propionic  acid  from, 

183 

"Circulating"  protein,  85 

Circulation,  disturbances  of,  and  non- 
protein nitrogen  of  blood,  496 

Citron  and  Leschke,  510 

Clapp,  Charles,  338 

Clark,  see  Tracy,  210 

Climate 
and  racial  characteristics,  148 
and  work,  effect  of,  upon  metabol- 
ism of  fat  in    individual,   table, 

effect  upon  metabolism,  150 
Clothing 
and  heat  regulation,  148 
influence  of,  upon  metabolism,  table, 
149 
during  exercise,  313 
Cocoa,   effect   of,   on   purin   bases   in 

urine,  532 
Cod-liver  oil,  influence  on  growth,  369 


Coffee 
effect  of 

in  fatigue,  325 
on  purin  bases  in  urine,  532 
Cohn, 535 
Cold 
exposure  to,  and  glycosuria,  448 
influence  of,  upon  sugar  excretion  in 
pancreatic  diabetes,  457 
in  phlorhizin  glycosuria,  457 
Cole,  see  Hopkins,  206 
Coleman,  Barr,  and  Du  Bois 

body     temperature    and    heat 
production  in  erysipelas,  509 
Coleman  and  Du  Bois 

basal  metabolism  in  typhoid,  518 
body  temperature 

and  metabolism  in  typhoid, 

5°7,  509 
measurement  in  fever,  133 
effect  of  bodily  activity  on  basal 

metabolism  in  typhoid,  519 
nitrogen  equilibrium  in   typhoid, 

5J4 
respiratory  metabolism  in  typhoid, 

5i7,  5-9° 
Coleman  and  Gephart,  absorption  of 

food  in  typhoid,  520 
Coleman,  see  Shaffer,  516 
Coma 
and  /^-oxybutyric  acid,  465 
hydrogen-ion  concentration  of  blood 
in,  table,  468 
Compensation  theory,  236 
Compounds,  carbon,  origin  of  chemis- 
try of,  20 
Coolen,  452 
Corn  and  pellagra,  366 
Corn  meal,  influence  of,  upon  growth, 

370, 374 
Corpora  striata,  effect  of  puncture  of, 

5°3 
Cost 

of  food 

at  boys'  boarding  school,  558 

in  Childs'  restaurants,  table,  563, 

569 
for   family   in   New   York    City, 
table,  560 
of  protein  and  energy,  table  show- 
ing, 575 
of  United  States'  food  supply,  557 
wholesale,  of  food  supply  for  Ger- 
many, table,  557 
Cotton-seed  oil,  influence  of,  on  growth, 

369 
Cramer,  461 

Cramer  and  Krause,  442 
Crawford,  ^^ 


INDEX 


595 


Creatin 

action  of  arginase  on,  205 

and  carbohydrate  metabolism,  212, 

213 
creatinin  from,  211 
excretion 

and  carcinoma  of  liver,  212 
and  cellular  destruction,  212 
of,  in  fasting,  92,  93 
after  parturition,  212 
and  phosphorus  poisoning,  212 
after  removal  of  uterus,  212 
fate  of,  ingested,  211 
from  guanidin  acetic  acid,  205 
in  muscle  with  carbohydrate  diet, 

213 
in  muscles  of  various  species,  211 
occurrence,  211 
in  urine,  212 
Creatinin 

co-efficient,  210 
from  creatin,  211 
elimination 

and  basal  metabolism,  211 
constant,  209 
of,  exogenous,  210 
in  fasting,  92,  93 
on  low  protein  diet,  272 
in  phosphorus  poisoning,  210 
of,  during  muscular  work,  210,  317 
liver,  in  production  of,  210 
and  muscular  development,  210 
nitrogen  :  total  nitrogen,  209 
Cremer 

fat  from  protein,  229 
fat  sparing  by  rhamnose,  488 
glucose  from 
glycocoll,  190 
ingested  glycerin,  457 
pyruvic  acid,  192 
lactose  in  milk  in   phlorhizin   dia- 
betes, 395 
muscle  glycogen  after  lean  meat  in- 
gestion, 229 
silicic  acid  as  feces  marker,  48 
p-Cresol,  excretion  of,  207 
Cretin,    metabolism    of,    calorimetric 

observations,  table,  442 
Cronheim,  160 

Crying,   energy   expended   by,   in   in- 
fants, 407 
Csonka,  188,  242 
see  Edelstein,  398 
see  Janney,  456 
Curare,  effect  of,  upon  oxygen  absorp- 
tion at  various  temperatures  in  dog, 

"5 
Cushing,  438 
Cushing  and  Goetsch,  439 


Cushny,  A.  R.,  see  Benedict,  F.  G.,  358 
Cyanosis,   and   alveolar  oxygen  pres- 
sure, 433,  434 
Cystein 

from  cystin,  199 

glucose  from,  200 

influence  of,  upon  growth,  277 

metabolism  of,  200 

serin  from,  200 

sulphur  excretion  from,  200 

taurin  from,  179,  199 
Cystin 

cystein  from,  199 

elimination  in  cystinuria,  198 

fate  of,  198 

glucose  from,  198 

in  normal  metabolism,  199 

occurrence,  198 
Cystinuria,  198 

cystin  elimination  in,  198 

induced,  199 
Cytosin,  structure  of,  527 
Czerny,  497 
Czyhlarz  and  Fuchs,  491 


DAKIN 

action  of  arginase,  205 

arginin,  204 

aspartic  acid  metabolism,  201 

biochemical 

interconversions,  scheme  for,  266 

relations  of  amino-acids,  177 
cystein,  pathway  of  destruction  in 

body,  200 
excretion  of  benzoate,  185 
histidin,  205 
homogentisic  acid,  196 
leucin,  195 
lysin,  203 

methyl  glyoxal,  194 
ornithin,  204 
/3-oxy -propionic  acid,  183 
phenyl-alanin,  197 
phenyl-/3-oxy -propionic  acid,  183 
prolin,  205 
serin,  198 
tryptophan,  205 
tyrosin,  197 
valin,  195 
Dakin  and  Dudley 

glucose  from 
1-alanin,  191 

methyl-glyoxal    and    1-lactic 
acid,  193 

lactic  acid   from  methyl-glyoxal, 
192,  265 
Dakin  and  Janney,  glucose  from  pyru- 
vic acid,  192 


596 


INDEX 


Dakin,  Janney,  and  Wakeman,  formic 

acid  in  urine,  208 
Dakin  and   Wakeman,  production  of 

/2-oxybutyric  acid,  197 
Dakin,  sec  Kossel,  203 

see  Wakeman,  466 
Dalmatian  hound,  uric  acid,  peculiar- 
ity in,  537 
"Darmarbeit,"   experiments   on,    231, 

232 
Daval,  see  Patein,  399 
Davis  and  Foster  496 
Davis,  see  Marshall,  165 

see  McCollum,  369,  370 
Deamination 
how  effected,  176 
hydrolytic,  177 

evidence  of,  181,  182 
oxidative,  177 

and  CO2  cleavage,  179,  180 
of  alanin,  178,  179 
probable  reaction  of,  179 
primary  pathway  of,  178 
process  of,  177 
proof  of  early,  186 
reversible,  198 

successive  stages  of,  180,  181 
summary  of  various  means  of,  181 
Dean,  see  Henderson,  158 
Death,  cause  of,  from  starvation,  102, 

103,  104 
"Deficiency  diseases,"  362 
Degeneration 

fatty,  in  fevers,  521 
parenchymatous,  521 
Delbrueck,  285 
Denis 
effect  of  drugs  on  uric  acid  in  urine 

and  blood,  549 
uric  acid  in  blood  after  ingestion  of 

foods  rich  in  purin,  549 
see  Folin,  79,  94,  449,  495,  547 
Denis   and    Means,   effect   of   sodium 

salicylate  on  uric  acid  excretion,  549 
"Deposit"  protein,  84,  169 
and  "circulating,"  85 
and  tissue  protein,  276 
elimination  of,  84 
estimation  of,  210 
how  retained,  287 
in  fasting,  85 
Depretz,  34 

Descent,  metabolism  during,  330 
Development 
energy  for,  379 
muscular  and  creatinin,  210 
physical  and  protein  allowance,  341, 
342 
Dextrose  and  nitrogen  ratio,  see  D  :  N. 


Diabetes,  see  Glycosuria. 

Allen  treatment  of,  as  applied  by 
Joslin,  482 
advantages  of,  483 
acidosis  in,  464,  475 
and  extirpation  of  pancreas,  446 
blood  reaction  in,  how  maintained, 

221 
carbon  monoxid,  462 
comparison  of  metabolism  of,  with 

normal,  table,  473 
complete  picture  of,  479 
definition  of,  445 
effect  of 

blood  transfusion  upon,  484 

ingestion  of  yeast  on  D  :  N  ratio 
in,  485 
experimental,    in    various    animals, 

D  :  N  table,  455 
fasting  in,  479 
fat  deposits  in  liver  and  muscles  in, 

489 
fate  of  ingested  /3-oxybutyric  acid 

in,  465,  466 
glucose 

and  nitrogen  excretion  after  meat, 
172 

from  fat  in,  457,  458 

from  glycerin  in,  457 
glycogen  from  glucose  in  liver  in,  448 
heat  production  in,  473,  474,  475 
hydrogen-ion  concentration  of  blood 

in,  table,  468 
individual  variations  in,  469,  470 
influence  of 

emaciation  upon  metabolism  of, 
table,  476 

on  protein  metabolism,  table,  463 
metabolism 

in,  chapter,  445 

of  patient  while  fasting,  table,  481 
oatmeal  treatment  of,  efficiency  of, 

483 

origin  of  glucose  in,  175 

pancreatic,  influence  of 

cold  upon  sugar  excretion  in,  457 
mechanical  exercise  on  sugar  ex- 
cretion in,  457 

pathology  of  pancreas  in,  488 

phlorhizin,  D  :  N  in,  table,  99 

protein 

and  fat  alone,  in  treatment  of,  479 
metabolism  of,  influence  of  thy- 
roid on,  460 

respiratory  quotient,  calculation,  470 

role  of  thyroid  in,  459 

severe 

a  case  of,  464 

metabolism  of,  table,  469 


INDEX 


597 


Diabetes 

severe 

D  :  N  ratios  during  treatment,  479 
fructose  in  urine  during,  446 
metabolism  of,  table,  477 
non-protein   respiratory   quotient 

in,  471 
partition  of  aceton  bodies  in,  466 
protein  metabolism  in,  463,  464 
reaction  of  blood  in,  table,  221 
recovery   fron,    clinical   and     ex- 
perimental data,  chart,  478 
respiratory  quotient  for  fat  in,  472 

and  starvation,  447 

sugar  from 
gelatin  in,  156 
protein  in,  172 

urinary  nitrogen,  caloric  value  of,  471 

use  of 

alcohol  in  treatment  of,  480 
fructose  in  treatment  of,  485,  486 
opium  in  treatment  of,  485 
pentoses  in,  488 
Dialysis,  82 
Diamino  nitrogen,  78 
Diaminuria,  203 

Diazo  reaction,  from  histidin,  205 
Dietaries 

deficient,  364 

hospital,  351 

standard,  350 
Dietrich,  see  Voeltz,  357 
Diets 

alcohol-ether  extracted,  364 

and  altitude,  433 

and  content  of,  358 

calcium  in,  359 

in  diabetes,  482 

climate  and  choice  of,  344 

energy  distribution  in,  345 

for  farmers,  348 

in  fever,  515 

in  gout,  551 

for  Finnish  peasant,  348 

food  values  of,  353 

Hindhede's,  340 

iron  in,  360 

for  Italian  peasant,  342 

for  laborer,  335 

for  lumbermen,  348 

milk  alone,  353 

and  milk  secretion,  391,  394 

mixed,  42,  239,  280 

normal,  334 

in  a  poorhouse,  351 

in  pregnancy,  384 

purin-free,  540 

chemical  comparison  of  urines  on, 
574 


Diets 
protein 

high,  275,  337 
low,  337-347 

when  contraindicated,  312,  344 
in  thyroid  disease,  443 
in  various  occupations,  346 
water  loss  from  body  in  changing, 

272 
and  work,  as  factor  in,  311 
Digestibility  of  carbohydrates,  52 
Digestion 
amino-acids,  rapidity  of,  242,  243 
protein,  rapidity  of,  242,  243 
Digitalis,    influence    of,    upon    basal 
metabolism   of,  in   cardiac  disease, 
554 
Dinucleotid,  531 
Dioxyaceton   from   glycerol,   reaction, 

262 
Disaccharids,  absence  of,  in  diabetic 

urine,  446 
Diseases,    intestinal,    elimination    of 

fecal  nitrogen  in,  52 
Diuresis,  231 
D  :  N 
constancy  of,  table,  174 

after  meat  ingestion,  456,  457 
in  depancreatLzed  dog,  454 
in  diabetes  mellitus,  455 
effect  of  ingestion  of  yeast  upon,  in 

diabetes,  485 
in  experimental  diabetes  in  animals, 

_  table,  455 
high,   continued  in   phlorhizin   gly- 
cosuria, explanation  of  after  thy- 
roidectomy, 461 
high  ratios  of,  458,  450 
influence  of  metabolism  of  fat  upon, 

457. 
after  ingestion  of  various  forms  of 

protein,  table,  456 
after  phlorhizin,  454 
in  phlorhizin  diabetes 

after  meat  ingestion,  table,  172 
in  starvation,  table,  99 
in  phlorhizinized  dog,  table,  455 
in  phlorhizinized  man,  table,  455 
ratio,  explanation  of  diverging,  461, 

462 
ratios  during  treatment  of  a  severe 

case  of  diabetes,  479 
theoretical  calculation  of,  207 
Dobson,  445 
Dock,  446 

Doerpinghaus,  see  Abderhalden,  102 
Douglas,    Haldane,    Henderson,    and 

Schneider,  427,  430 
Dox,  see  Eward,  374 


598 


INDEX 


Drugs 

effect  of,  on  uric  acid  elimination, 

549 
influence  of  various,  on  metabolism, 
table,  553 
Du  Bois,  D.,  and  E.  F.  Du  Bois,  124, 

125 
Du  Bois,  E.  F. 
absorption  of  food  in  typhoid  fever, 

52° 
calorimetric  studies  in  thyroid  dis- 
ease, 441 
metabolism  of  a  dwarf  after  meat 

ingestion,  247 
standards  of  basal  metabolism  with 

regard  to  age  and  sex,  127 
see  Allen,  471,  474,  475 
see  Aub,  127 
see  Coleman,  133,  507,  509,  514,  517, 

518,  519 
see  D.  Du  Bois,  124,  125 
see  Eggleston,  554 
see    Gephart,    127,    131  ,  247,    290, 

381 
see  Geyelin,  477 
see  Means,  554 
see  Meyer,  A.  L.,  424 
see  Peabody,  497 
Du  Bois  and  Veeder,  heat  production 

in  a  diabetic,  473 
Du  Bois-Reymond,  R.,  ^^^ 

and  L.  Zuntz,  ^^^ 
Dudley,    see    Dakin,     191,    192,    193, 

265 
Dulong,  34 

Dumas,  see  Provost,  495 
Durig,  see  Toegel,  290,  357 
Durig    and    Grau,    effect    of    electric 
energy   on   heat   production   in   or- 
ganism, 150 
Durig  and  Zuntz 

Cheyne-Stokes  respiration  at  high 

altitude,  430 
composition     of    atmosphere     at 

high  altitude,  427 
effect  of  climate  on  basal  metab- 
olism, 150 
hemoglobin  in  blood  at  different 

altitudes,  432 
metabolism 

at  high  altitudes,  437 
during  mountaineering,  428 
Dwarf,  122,  247,  442 
"Dynamic  quota,"  of  protein,  defini- 
tion of,  277 
Dyspnea,  effect  upon  metabolism,  423, 

407 
Dystrophia     adiposogenitalis,     metab- 
olism in,  438 


VAN    ECKENSTEIN,    see    Lobrey    de 

Bruyn,  260 
Eck  fistula,  22,  447,  451 
Edelmann,  see  Murlin,  473 
Edelstein  and  Csonka,  398 
Edestin 

comparative  value  of,  in  growth,  376 
glucose  derivable  from,  457 
Edkins,  see  Langley,  105 
Egg 

heat  production  in,  during  incuba- 
tion, 379,  380 
protein  of,  during  incubation,  380 
respiration  of,  380 
Egg  yolk,  influence  on  growth,  369 
Eggleston  and  Du  Bois,  554 
Eggs,  fundulus,  heat  production  in,  380 
Ehrlich,  F.,  180,  202 
Eijkman,  362 

Einbeck,  see  Abderhalden,  205 
Elberstadt,  423 

Electric  check,  definition  of,  56 
Elias,  447 

Elias  and  Kolb,  447 
Ellinger,  205 

Ellinger  and  Matsuoka,  206 
Emaciation 

factor   of,   in   selection  of   "normal 

controls,"  476 
heat  production  during,  406 
influence    of,    upon    metabolism   in 
diabetes,  table,  476 
Emanations,  radio-active,  action  of,  in 

gout,  550 
Embden,  lactic  acid  in  liver,  263 
Embden    and    Baldes,    tyrosin    from 

phenylalanin,  195 
Embden,  Baldes,  and  Schmitz,  forma- 
tion of  lactic  acid  by  red  blood  cells 
of  cattle,  265 
Embden  and  Engel,  aceto-acetic  acid 

from  ,?-oxybutyric  acid,  466 
Embden,     Griesbach,     and     Schmitz, 
lactic  acid  formation  in  tissues,  264 
Embden,  Kalderlah,  and  Engel,  lactic 

acid  formation  in  tissues,  264 
Embden  and  Salomon,  D  :  N  ratio  in 

depancreatized  dogs,  454 
Embden,  Salomon,  and  Schmidt 
aceton  bodies  from 
leucin,  195 

phenylalanin,  tyrosin,  homo- 
gentisic  acid,  and  muconic 
acid,  197 
valin,  194 
Embden  and  Schmitz 

alanin  from  pyruvic  acid,  194 
phenyl-alanin    and    tyrosin   from 
keto-acids,  198 


INDEX 


599 


Embden,  Schmitz,  and  Wittenberg 

cleavage  of  glucose  and  fructose, 
265 
Embryo,  influence  of  pancreas  of,  after 

pancreatectomy  in  mother,  453 
Emerson,  569 
Emmes,  see  Benedict,  F.  G.,  127,  232, 

383 
Endurance  in  fasting,  97 
Energy 

for  development,  379 

in  dietaries  for  various  occupations, 

.  349 

distributions  of,  in  various  dietaries, 

table,  345 
from  fat  in  starvation,  86 
law  of  the  conservation  of,  34,  35, 

320 
metabolized    in    different    animals 

from    maturity    to   death,    table, 

416 
normal  requirement  of,  in  growth, 

415 
"ontogenetic,"  379 
from   protein,   table   showing   cost, 

575 
relation  of  growth  to  ingested,  410, 

4-iij  4i3>  414 
requirement 

of  different  animals  in  performing 

same    amount    of    mechanical 

work,  table,  327 
in  early  starvation,  table,  90 
in  horizontal  walking,  influence  of 

velocity  and  load  upon,  table, 

328,  329 
of  men  of  various  weights  when 

doing  light  work,  table,  334 
in  undernutrition,  101 
retention  of 
for  growth,  412 
in  growth 

and  relation  of  fat  in  diet   to, 

4i5. 
in  various  animals,  415 
"Energy  expenditure,"  law  of,  413 
Engel,  see  Embden,  264,  466 
Enzymes 

action  of,  on  nucleic  acid,  529,  530 
deaminizing,   in   purin   metabolism, 

530,  531 
in  intestinal  mucosa,  258 
oxidizing  and  uric  acid  formation, 

531 
purin 

action  of,  533 
in  tissues,  533,  534,  535 
in  gout,  549 
Epidermis,  nitrogen  loss  through,  22 


Epinephrin 

and  emotional  glycosuria,  449 
glycosuria,  ease  of  production  of,  461 
respiratory  quotient  after  injection 
of,  460 

Eppinger,   Falta,   and   Rudinger,   458, 
460 

Epstein  and  Baehr,  448 

Equilibrium,  caloric,  how  maintained, 

239 
Erben, 524 

Erdmann  and  Marchand,  1S3 
Erdt,  219 

Eskimos,  treatment  of  scurvy  by,  365 
Ether  glycosuria,  462 
Ethylen-glycol,    from    oxy-aldehydes, 

191 
von  Euler,  269 
Evvard,  345 

Evvard,  Dox,  and  Guernsey,  374 
Ewing,  489 
Exercise,  see  Work. 

benefits  derived  from,  ^^ 

hard,  carbon  dioxid  tension  in  ar- 
terial blood  after,  322 

influence  of 

clothing  upon  metabolism  during, 

313 
on  excretion  of  purin,  542,  543 

temperature     upon     metabolism 
during,  313 
mechanical,  influence  of, 
on  sugar  excretion 

in  pancreatic  diabetes,  457 
in     phlorhizin     glycosuria, 
457,  458 
moderate 

carbon  dioxid  of  alveolar  air  after, 

322 
hydrogen-ion     concentration     of 
blood  after,  322 
Exophthalmic  goiter 

classification  in,  443 
conditions  in,  440 
metabolism    in,    calorimetric    ob- 
servations, table,  441,  442 
treatment  of,  443 
Extractives  in  milk,  399 


FAGAN,  see  Lauder,  395 
Falta 

homogentisic  acid  in  alcaptonuria, 

196 
rapidity  of  destruction  of  proteins, 
168 
Falta,  Grote,  and  Staehelin 

protein   metabolism   in   depan- 
creatized  dogs,  463,  474 


6oo 


INDEX 


Falta,  Grote,  and  Staehelin 

specific  dynamic  action  of  ca- 
sein   and    amino-acids    from 
casein,  239 
Falta 

see  Eppinger,  458,  460 
see  Neubauer,  196 
Family,  cost  of  food  for,  in  New  York 

City,  table,  560 
Farkas,  379 

Farmers,  dietaries  of,  table,  348 
Fast 

of  Breithaupt,  feces  in,  51 
of  Cetti,  feces  in,  51 
in  dogs,  record  of,  71 
metabolism  data  of  31-days',  96 
"repeated,"  protein  loss  in,  104 
Fasting 

acidosis  in,  table,  93 

albumin  in  urine,  92 

amino-acids  in  tissues  during,  82 

ash  balance  in,  table,  98 

bile,  105 

blood 

corpuscles  in,  106 
fat  during,  107 

plasma    nitrogen    during,    table, 
106 
body  temperature  during,  in,  112 
calcium  excretion,  92 
carbon  dioxid  elimination  in,  86 
creatin  excretion  in,  92,  93 
creatinin  excretion  in,  92,  93 
death  from,  102 
definition  of,  69 
"deposit"  protein  in,  85 
in  diabetes,  479 

effect  of  temperature  upon  metab- 
olism in,  table,  142 
endurance  in,  97 
excretion  of  ammonia  in,  92,  93 
faintness  in,  71 
fat 

content    of    milk    during,    table, 

•593 

in  liver  during,  249 

on  protein  metabolism,  100 

in  salmon  during,  249 
feces  in,  48 
gastric  juice  in,  105 
glycogen,  107,  206 

on  protein  metabolism,  table,  72, 

73 
heat  production  in,  97 
hemoglobin  in,  106 
length  of  life  in,  103 
meat,  previous  ingestion  of,  73 
mental  functions  in,  97 
metabolism,  89,  95 


Fasting 
nitrogen 

elimination  of 
in  dog,  72 
in  various  animals,  86 

excretion  in  prolonged,  91,  97 
/3-oxybutyric  acid  excretion  during, 

in  obesity,  94 
oxygen  absorption  in,  86 
pepsinogen  in  gastric  glands,  105 
potassium  excretion  in,  92,  93 
pulse  rate  in,  90 
urine 

magnesium  and  nitrogen,  98 

phosphorus  and  nitrogen,  92 

sulphur  and  nitrogen,  92 
weight  loss,  105 
work,  influence  of,  108 
Fat 

aceton  bodies  from,  in  organism,  250 
in  blood 

in  diabetes,  490 

during  fasting,  107 

after  fat  ingestion,  table,  251 

during  starvation,  249 
of  body,  how  regulated,  250 
and  carbohydrate  metabolism,  cal- 
culation of,  table,  61 
from  carbohydrate 

in  dog,  305 

in  geese,  305 

in  pig,  304 

reaction,  268,  306 

respiratory  quotient  of,  306 
carbon  from,  in  excretions,  40 
changes    in    phosphorus    poisoning, 

491 
during  cheese  ripening,  490 
"degeneration,"    explanation,    490, 

491 
deposits  of,  in  liver  and  muscles,  489 
in  diet,  relation  of,  to  energy  reten- 
tion in  growth,  415 
disappearance  of,  after  fat  ingestion, 

25* 
effect  upon  protein  metaholism  in 

starvation,  table,  100,  101,  103 
energy  from,  in  starvation,  86 
feeding,  source  of  heat  production 

after,  254 
glucose  from,  in  diabetes,  457,  458 
and  glycogen  antagonism,  249 
heat  production  after  ingestion  of, 

251,  232,  253 
human,  respiratory  quotient  of,  59 
influence  of 

upon  ammonia  excretion,  222 

environmental  temperature  upon 
metabolism  after  feeding,  252 


INDEX 


601 


Fat 

influence  of 

upon  feces,  49 

upon  growth,  369 

metabolism  of,  upon  D  :  N,  457 

upon  nitrogen  equilibrium,  254 

upon  nitrogen  retention,  table,  255 

upon  protein  metabolism,  248 
ingestion,  influence  of,  chapter,  248 
liver 

influence   of   carbohydrate   upon, 
249 

during  starvation,  249 
metabolism 

absence   of   "secondary   rise"   in, 
on  meat  fat  diet,  table,  256 

dynamic  aspects  of,  302 

after  ingestion  of,  251 

of,  during  work,  109,  318,  324 
in  milk,  390 

neutral,  ,^-oxybutyric  acid  from,  465 
nutritional  value 

calculation  of,  42 

of,  in  mixed  diet,  42 
oxidation  of,  1S2 
p'-oxy butyric  acid  from,  183,  250 
partial  replacement  of  carbohydrate 

by,  and  protein  metabolism,  270 
plethora,  301 
from  protein,  228,  229,  230 

by  calliphora,  230 
and  protein,  iso-dynamic  relations, 

257  ,  •     •   , 

replacement  of,  by  lactose  in  infant 

feeding,  412 

respiratory  quotient  of,  29,  58 

in  severe  diabetes,  472 

in  salmon  during  fasting,  249 

sparing  by  rhamnose,  488 

specific  dynamic  action  of,  table,  237, 

252,  3°i 
sugar  from,  472 

during  work,  319 
superficial,   effect  of,   upon  metab- 
olism of  dog,  table,  138 
"Fat  soluble  A,"  363 
Fatigue 
effect  of 

alcohol  in,  325 
coffee  in,  325 
upon  metabolism,  322 
oxygen  inhalation  on,  419 
stimulants  in,  325 
tea  in,  325 
Fatty  acids 

glucose  from,  184 
saturated,  oxidation  of,  183 
unsaturated,  oxidation  of,  183 
Fatty  infiltration  at  high  altitudes,  423 


Faulhorn,  metabolism  during  climbing 

of,  table,  315 
Feces 

bacteria  in,  55 

bacterial  nitrogen  of,  55 
in  rats,  55 

calculation  of  heat  value  of,  54 

caloric    value    of,    Rubner's    exper- 
iment, 39 

composition  of,   on  different  diets, 
table,  53 

derivation  of,  from  intestinal  excre- 
tions, 50 

fasting  in  human,  51 

of  herbivora,  comparison  with  car- 
nivora,  50 

heat  of  combustion  of,  53 

methods  of  period  separation  48 

nature  of,  47 

nitrogen  of 

in  health  and  disease  after  cane- 
sugar  feeding,  52 
from  nitrogen-free  food,  51 

normal,  definition  of,  53 

production  of,  on  meat  diet  in  dog, 

49 
in  relation  to  diet,  49 
undigested  residues  in,  54 
source  of,  49 
starch  in,  52 
starvation,  48 

after  vegetable  and  cereal  ingestion, 
52 
Feder,  163 

Feeding,  infant,  milk  in,  399,  400 
Fejes,  465 
Fellner,  194 

Fetus,  growth  of,  table,  389 
Fever 
aseptic 

definition  of,  499 
and  purin,  523 
body  temperature  and  heat  produc- 
tion in,  505,  506,  509 
causes  of,  500,  505,  506,  507 
classification,  499 

continuance  of,  suggestions  regard- 
ing, 510 
definition  of,  499 
degenerations  in,  521 
diet  in,  315 

effect  of  chill  in,  511,  512 
excretion  of  urea  in,  501 
high  metabolism  in,  experiments  on 

cause  of,  501,  520 
infective,  499,  504 
measurement  of  body  temperature 

in-  133 
metabolism  in,  chapter,  499 


602 


INDEX 


Fever 

metabolism    in,    induced  by  surra 
trypanosomes,  table,  504,  505 

neurogenic 

definition  of.  499 
example  of,  503 

hydrogen-ion     concentration     of 
blood  in,  504 

perspiration  in,  511 

physical    regulation   of   body   tem- 
perature in,  510,  511 

physiologic,  definition  of,  499 

protein  metabolism  in,  512,  515 

salt  retention  in,  522 

scarlet,  urine  in,  524 

toxins  in,  509 

typhoid 

absorption  of  food  in,  520 
basal  metabolism  in,  table,  518 
calorimetric  studies  in,  accuracy 

of,  table,  517 
carbohydrate   on  protein  metab- 
olism in,  table,  516 
heat  elimination,  relation  to  pro- 
duction of  decrease  in,   chart, 
508,  509 
heat  of  vaporizartion  of  water  in, 

511 
"high  calorie  diet"  in,  516 

nitrogen  balances  in,  table,  514, 

515  •       •       , 

protein  metabolism  in,  chart,  514 

purin  bases  in  urine  from,  524 

specific  dynamic  action  of  food  in, 

table,  510 

urine  in,  523 

water  retention  in,  522 
Fibrin,  glucose  derivable  from,  457 
Fick  and  Wislicenus,  315 
Fine,  see  Myers,  211,  213 
Fine  and  Chase,  549 
Fingerling,  394 

see  Morgen,  393 
Finkler,  421 

Finland,  dietaries  for  farmers  in,  348 
Fischer,  B.,  490 
Fischer,  Emil 

d-glucose  from  d-fructose,  261 

purin,  526 

structure  of  protein,  75,  175 
Fischler  and  Kosson,  466 
Fisher,  G..  and  Wishart,  291 
Fiske  and  Karsner,  221 
Fiske  and  Sumner,  81 
Fitzgerald,  436 
Flack,  see  Hill,  41Q 
Flavor  in  food,  value  of,  352 
Flesh,  definition  of,  153 
Fletcher  and  Brown,  264 


Fletcher  and  Hopkins,  420 
Folin 

composition    of    urine    on    various 

diets,  208 
creatin  in  urine  during  fasting,  212 
elimination  of  creatinin,  210 
reduction  of  protein  metabolism,  273 
Folin  and  Denis 

acidosis  in  obesity,  94 
non-protein  nitrogen  in  blood  in 

gout,  547 
urea  from  glycocoll,  79 
Folin,  Denis,  and  Seymour 

non-protein  nitrogen  in  blood, 

495 
Folin,  Denis,  and  Smillie 

emotional  glycosuria,  449 
see  Alsberg,  199 
Food 

absorption  of,  54 

in  typhoid  fever,  520 
accessories  and  purin  bases  in  urine, 

532 
acid  and  base  forming,  361 
action  of,  upon  basal  metabolism, 

301 
ash  content,  360 
bananas  as  exclusive,  355 
caloric  values  of,  37 
capacity  for  digestion  of,  344 
cell  mechanisms  for  influence  of,  303 
in  Childs'  restaurants,  caloric  value 

of,  table,  563-569 
cold,  effect  upon  metabolism,  table, 

123  • 

constituents,  retention  of,  by  mother 

and  child,  table,  389 

consumption  during  adolescence,  559 

cost  of 

for  family  in  New  York  City, 

table,  560 

2500  calories,  561 

definition  of,  152 

distribution  of  calories  in,  at  boys' 

boarding  school,  table,  560 

farinaceous,  and  scurvy,  365 

flavor,  value  of,  352 

growth  of  dogs  on  low  energy  in, 

4J5 

"ideal,"  definition  of,  152 

indigestible,  value  of,  54 

influence  of,  on  uric  acid  excretion, 
54o 

intoxication  of,  in  infants,  and  am- 
monia excretion,  220 

needed  by  old  men,  351 

nutritive  values,  362 

"patent,"  value  of,  352 

purified,  and  offspring,  362 


INDEX 


6o- 


Food 

relation  of  growth  to,  ingested,  410, 

411,  413,  414  _ 
requirement  during  growth,  chapter, 

379 
selection  of,  influence  of  appetite  on, 

345 

specific  dynamic  action  of,  239,  519 
statistics,  municipal,  table,  350 
value  of  labeling  according  to  con- 
tent, 562 
Food  economics,  chapter,  555 

importance  of,  555 
"Food  hormone,"  364 
Food  labels,  improvement  of,  562 
Food  laws,   enforcement   of,   in   Ger- 
many at  present  time,  556 
Food   production  in   Germany  during 

1014-1916,  556 
Food  requirements  of  Germany,  table, 

556 
Food  supply 

for  Germany,  555 

per  meal  in  boys'  boarding  school, 

table,  558 
United  States,  cost  of,  557 
Food  value 

of  dietary,  calculation  of,  353 
of  Liebig's  extract  of  beef,  352 
Food-stuffs 

definition  of,  152 
enumeration  of,  152 
iso-dynamic  quantities  of,  37 
Liebig's  original  theory  concerning 

oxidation  of,  20 
ordinary,  composition  of,  576-584 
purified,  influence  of,  upon  growth, 

summary,  370 
rationality  of  non-nitrogenous  mix- 
ture, 275 
specific  dynamic  action  of,  chart,  237 
standard  values  of,  Rubner,  42 
Formic  acid  in  urine,  208 
Forschbach,  parabiosis  and  diabetes, 

453 
Forschbach  and  Severin 

glycosuria  in  exophthalmic  goiter, 

442 
hyperthyroidism  and  disturbance 

of  pancreas,  459 
hypoglycemia  in  affections  of  the 
hypophysis,     439 
Forssner,  250 
Forster,  74 
Foster,  445,  496 
see  Davis,  496 
Fraenkel  and  Geppert,  427 
Frank  and  Trommsdorff,  223 
Frank  and  Voit,  120 


Frankel,  see  Ringer,  201,  202,  203 

Freise,  296 

Frentzel,  108 

Frentzel  and  Reach,  326 

Freund,  E.  and  O. 

Succi's   nitrogen   excretion  in  star- 
vation, 90,  91 
nitrogen   :  phosphoric  acid  ratio  in 
starvation,  92 
Freund,  H.,  heat  puncture  after  sever- 
ing cord,  503 
Freund   and    Marchand,   blood    sugar 
and    low    environmental    tem- 
perature, 145,  457 
piqure  and  adrenals,  447 
Friedjung,  see  Jolles,  398 
Friedmann,  199 
Fries,  421 

see  Armsby,  51 
Froelich,  see  Hoist,  364 
Frog 

anaerobic,  metabolism  of,  420 
elimination  of  carbon  dioxid  in,  at 
various  temperatures,  curve,  114 
Fromherz,  see  Neubauer,  179,  180 
Fromherz  and  Hermanns,  196 
Fructose 

carbon  dioxid  output  after  ingestion 

of,  peculiarity  of.  289,  294 
fate  of,  in  bod}',  258 
glucose  from,  194,  261 

by  liver  perfusion,  259 
glycogen  from,  448 
ingested,  258 
after  injection  of,  259 
influence  of 

upon  glucose  tolerance.  486 
in  phlorhizin  glycosuria,  table, 
296 
intermediary  products  in  conversion 

into  glucose,  264,  295,  296 
metabolism    of,   as   compared   with 

glucose,  290 
methyl-glyoxal  from,  194 
urinary,  in  severe  diabetes,  446 
use  of,  in  treating  diabetes,  485,  486 
Fruit  juices,  use  of,  in  scurvy,  365 
Frumerie,  322 
Fuchs  and  Roth,  460 
Fuchs,  see  von  Benczur,  550 

see  Czyhlarz,  491 
von  Fuerth 

acetylation  in  the  organism,  199 
chromogen  of  urochrom,  205 
diaminuria,  203 

effect   of  glucose   upon  lactic   acid 
excretion   in   phosphorus   poison- 
ing, 263  _ 
lactic  acid  in  tissues,  263 


604 


INDEX 


Functions,  mental,  in  fasting,  97 
Fundulus,   eggs,   heat   production   in, 

380 
Funk,  C. 
pellagra  statistics  in  United  States, 

366_ 
vitamins,  363 
yeast  vitamins 

and  beri-beri,  367 
and  polyneuritis,  367 
Funk,  C,  and  A.  B.  Macallum,  energy 
of  growth,  414 


Galactose 
fate  of,  in  body,  258 
glucose  from,  194 
glycogen  from,  258,  259 
leukocytes  and,  264 
Galambos  and  Tausz,  464 
Galeotti,  433 
Gamble,  see  Palmer,  211 
Garrod,  544 
Garrod  and  Hele,  196 
Gases 
alveolar,  tension   of,  in   acclimated 

individuals,  table,  437 
respiratory,  heat  value  of,  62 
Gastric  juice  in  starvation,  105 
Geelmuyden,  446 
Gelatin 

deficiencies  in,  157 
endogenous  protein  sparing  by,  283 
glucose  derivable  from,  156,  457 
glycogen  production  from,  283 
influence  of,  in  metabolism,   table, 

281 
metabolism    and    kynurenic    acid, 

206 
as  protein  sparer  in  phlorhizinized 

dog,  table,  282 
protein  sparing  action  of,  85,  373 

in  mixed  diet,  table,  280 
replacement    of    protein    by,    156, 

iS7 
sparing  power,  explanation  of,  280, 
281,  283 
Gemelli,  439 
Genter,  see  Jordan,  393 
Gephart,  F.  C. 
dietary  study  of  St.  Paul's  School, 
558 
Gephart  and  Du  Bois 

basal  metabolism  of  normal  con- 
trols, 127 
heat  production  after  ingestion  of 

glucose,  290 
increase  in  metabolism  after  meat, 
247 


Gephart  and  Du  Bois 

oxidative    process    during    men- 
struation, 381 
water  loss  from  lungs  and  skin,  131 
Gephart  and  Lusk 

analysis    and    cost    of    ready-to- 
serve  foods,  563 
Gephart,  F.  C,  see  Coleman,  520 
Geppert,  425 

see  Fraenkel,  427 
Germany 

present  enforcement   of  food  laws, 
556 

food  requirements  of,  table,  556 

food  supply  for,  555 

during  1914-1916,  556 

wholesale  cost  of  food  supply  for,  557 
Gettler,  see  Sherman,  360,  361 
Gettler  and  Baker,  495 
Geyelin  and  Du  Bois,  477 
Gibson, 113 
Gies,  see  Hawk,  421 
Gilbert  and  Baudouin,  291 
Givens,  see  Hunter,  367,  536,  537 
Glands,  activity  of,  in  starvation,  105 
Glaser,  380 
Gliadin 

effect  of  ingested,  upon  blood  pro- 
teins, 160 

glucose  derivable  from,  457 

influence  of,  upon  growth,  375 
Globulin,     squash-seed,     comparative 

value  of,  in  growth,  376 
Glucose 

absorption  and  combustion  of,  290 

and  adrenalin  injections,  458 

from  d-alanin,  191 

from  d-1-alanin,  194 

from  1-alanin,  191 

from  amino-acids,  184 

rapidity  of  elimination  of,  242 

from  arginin,  203,  204 

from  aspartic  acid,  200,  201 

in  bile  after  phlorhizin,  451 

in  blood  in  anemia,  421 

from  casein,  457 

a-colloid  in  blood,  462 

b-colloid  in  blood,  462 

from  cystein,  200 

from  cystin,  108 

in  diabetic  urine,  446 

from  edestin,  457 

elimination  of,  table,  189 

excretion  of,  by  depancreatized  dog, 
after  "nutrose"  feeding,  456 

in  diabetes,  457,  458 

effect  of  ingestion  of,  upon  heat  pro- 
duction, chart,  253 

fate  of,  in  body,  258 


INDEX 


60: 


Glucose 
from  fat,  319,  472 
from  fatty  acids,  184 
ingestion 

effect  upon  blood  sugar,  291 
influence  upon 

dilution  of  blood,  292 

urine  volume,  table,  291 
from  fibrin,  457 
from  fructose,  194 

by  liver  perfusion,  259 
d-fructose  from,  260 
from  galactose,  194 
from  gelatin,  457 
from  gliadin,  457 
from  glutamic  acid,  201 
from  glyceric  acid,  193 
from  glyceric  aldehyd,  193 
glyceric    aldehyd    as    intermediate 

metabolite  of,  reaction,  265 
from  glycerin,  457 
from  glycocoll,  table,  184,  188,  189 

how  formed,  reaction,  189,  190 

in    phlorhizin    glycosuria    with 
Eck  fistula,  451 
from  glycogen,  324 
glycogen  from 

in  diabetic  liver,  448 

after  injection  of,  259 
from  histidin,  205 
hydrogen-ion      concentration      and 

utilization  of,  by  heart,  261 
increase  in  heat  production  after  in- 
gestion of,  table,  290 

cause  of,  293,  294 
invulnerability  of,  in  diabetes,  261 
from  lactic  acid,  262 
lactic  acid  from,  proof  of,  263 
from  d-lactic  acid,  191 
from  d-1-lactic  acid,  191 
from  1-lactic  acid,  193 
from  leucin,  195 
and  leukocytes,  264 
from  lysin,  203 
from  malic  acid,  201 
d-mannose  from,  260 
metabolism  of,  307 

as  compared  with  fructose,  290 
from  methyl-glyoxal,  193 
methyl-glyoxal  from,  266 
and  nitrogen  elimination  in  diabetes, 

table  and  curve,  173 
optical  activity  loss  in  alkaline  so- 
lution, 261 
origin  of,  in  diabetes,  175 
from  ornithin,  204 
from  ovalbumin,  457 
oxidation  of.  267 
palmitic  acid  from,  reaction,  268 


Glucose 

from  phenylalanin,  197 

early  production  from  protein,  1 74 

from  prolin,  205 

from  protein 

calculation  of,  table,  207 
quantitative  relation,  174 

d-pseudo-fructose  from,  260 

from  pyruvic  acid,  192 

quantities  of,  from  various  proteins, 

456,  457 
retention  of,  232 
from  1-serin,  198 
from  serum  albumin,  457 
from  succinic  acid,  202 
and  tissue  extracts,  264 
from  tryptophan,  205 
from  tyrosin,  197 
urinary,  in  anemia,  421,  422 
utilization,    effect    of    parathyroid- 
ectomy on, 444 
from  valin,  195 
from  zein,  457 
Glucuronic  acid,  how  formed,  486,  487 
Glutamic  acid 

from  butyric  acid,  462 

fate  of,  201 

glucose  from,  201 

glyceric  acid  from,  202 

occurrence,  201 

pyrrolidon  carboxylic  acid  from, 
202 

specific  dynamic  action  of,   240, 

241 . 
succinic  acid  from,  202 

Glutelin,  influence  of,  upon  growth,  373 

Gluten,  corn,  influence  of,  upon  growth, 

374 
Glyceric  acid 

glucose  from,  193 
from  glutamic  acid,  202 
1-lactic  acid  from,  262 
from  1-serin,  198 
Glyceric  aldehyd 

glucose  from,  193 

as     intermediate     metabolite     of 

glucose,  reaction,  265 
from  1-serin,  198 
Glycerol 
dioxyaceton  from,  reaction,  262 
glucose  from,  457 
Glycinin,  soy  bean,  comparative  value 

of,  in  growth,  376 
Glycocoll 
effect  of 

upon    metabolism    in    phlorhizin 

diabetes,  table,  244 
upon    oxygen    absorption    under 
normal  conditions,  245 


6o6 


INDEX 


Glycocoll 

elimination  of,  185,  186,  187 

fate  of,  184 

glucose  from,  184,  188 
how  formed,  190 
in    phlorhizin    glycosuria   with 

Eck  fistula,  451 
reaction,  189,  190 
table,  189 

glucose  and  fat,  severally  and  to- 
gether, effect  upon  metabolism, 
table  and  chart,  299,  300,  301 

occurrence,  184 

origin  of,  186,  187,  188 

production  of,  and  gelatin,  283 

specific  dynamic  action  of,  240, 
241 

value  of,  188 
Glycogen 

alanin  from,  194 

from  alanin,  191     * 

in  body  after  carbohydrate  inges- 
tion, 259 

body  after  phlorhizin  injections,  107 

in  diabetic  liver,  448 

discharge  of,  and  epinephrin,  449 

distribution  of,  in  various  organs 
after  carbohydrate  feeding,  table, 
259,  260 

and  fat,  antagonism,  249 

from  fructose,  258,  448 

from  galactose,  258,  259 

from  glucose,  259 

in  heart  during  starvation,  260 

influence  on  protein  metabolism,  in 
fasting,  72,  73 

d-lactic  acid  from,  in  liver  perfusion, 
263 

and  la  piqure,  446 

liver 

discharge  of,  effect  of  acids  upon, 

447 

effect  of  hydrazin  upon,  494 
metabolism  of,  after  cold  baths,  144 
persistence  of,  in  body,  260 
from  protein,  171 
removal  of,  from  body,  107 
retention 

and  diphtheria  toxin,  522 

in  hyperthyroidism,  442,  443 
source  of,  in  body,  258 
in  starvation,  107,  260 
storage  of,  and  acidosis,  447 
and  strychnin  on,  107 
sugar  from,  effect  of  acid  formation 

upon, 324 
Glycollic    acid,   and   specific   dynamic 

action,  245 
Glycolysis,  explanation  of,  264 


Glycosuria,  see  Diabetes. 
alimentary,  449,  450 
asphyxial,  influence  of  acids  in,  447 
cold  and,  448,  457 
"emotional,"  449 

epinephrin,  ease  of  production  of,  461 
after  ether  inhalation,  462 
from  exposure  to  cold,  448 
pancreatic 

observations  on  partial  removal  of 

pancreas  in,  453 
specific  dynamic  action  of  protein 
in,  474 
phlorhizin,  99,  172,  188,  450 
cold  and,  457 
in  dogs,  D  :  N,  455 
and  Eck  fistula,  451 
in,  explanation  of  high  continued 
D   :  N  ratios   after   thyroidec- 
tomy, 461 
glucose  from  glycocoll  with  Eck 

fistula,  451 
in,  ingested  sugar,  fate  of,  451,  452 
in  man,  D  :  X,  455 
metabolism     in,     after     thyroid- 
ectomy, 460,  461 
renal,  character  of,  450,  451 
specific  dynamic  action  of  protein 

in,  474  . 
spleen  extirpation  in,  451 
transitory,  nature  of,  452 
work  and,  457 
Glycosurias,  classification  of,  450 
Glycyl-glycin,  urea  from,  176 
"Glyoxylases,"  193 
Goetsch,  see  Cushing,  439 
Gogitidse,  394 
Goiter,  exophthalmic,  metabolism  in, 

chapter,  418 
Goldberger,  366 
Goldbraith  and  Simpson,  113 
Goldschmidt,  see  Underbill,  284 
Gout,  chapter,  526 
action  of,  radioactive  emanations  on, 

55° 
dietary  treatment  of,  551 
differential  diagnosis  from  arthritis, 

547 
discovery  of  uric  acid  in  blood  in,  544 
early  description  of,  544 
effect  of  ingestion  of  nucleoprotein 

on  uric  acid  elimination  in,  547 
elimination  of  injected  uric  acid  in, 

548 
metabolism  in,  544 
non-protein  nitrogen  in  blood  in,  547 
purin 

enzymes  in  tissues  in,  549 

tolerance  in,  table,  550,  551 


INDEX 


607 


Gout 

summary  of  modern  knowledge  con- 
cerning, 545,  546,  547 

uric  acid 

in  blood  in,  547 
retention  in,  548 
in  urine  in,  table,  548 
Gradient,  effect  of,  upon  metabolism, 

during  muscular  work,  330 
Grafe 

aceton  bodies  in  fasting,  94 

heat  production  after  excessive  car- 
bohydrate feeding,  306 

metabolism 

in  leukemia,  424 
in  stupor,  438 

oyxgen  absorption  after  glycocoll  in- 
gestion, 245 

protein    sparing    with    ammonium 
citrate,  284 

respiratory  metabolism  in  typhoid, 

specific  dynamic  action  after  giving 
amino-acids,  247 
Grafe  and  Graham,  metabolism  after 

meat  ingestion,  130 
Grafe  and  Schlaepfer,  synthetic  pro- 
duction of  protein,  284 
Grafe    and    Turban,    protein    sparing 

with  urea,  284 
Graham  and  Poulton,  501 
Graham,  see  Grafe,  130 
Graham,  Sylvester,  338 
Grain 

influence  of  various  kinds  of,  upon 
growth.  37c 

unmilled,  and  scurvy,  365 
Grau,  see  Durig,  150 
Green,  see  Cathcart,  169 
Greene,  249 
Greenwald,  455 

Griesbach  and  Oppenheimer,  176 
Griesbach,  see  Embden,  264 
Grimmer,  391 
Groebbels,  355 

Grote,  see  Falta,  239,  463,  474 
Growth 

and  alcohol-ether  extracted  diet,  364 

calcium  in,  412 

capacity    for,    and    stimulation    of 
metabolism,  413 

in  children,  relation  of,  to  milk  in- 
gested, 410 

of  dogs  on  low  energy  diet,  415 

energy  retention  in,  and  relation  of 
fat  in  diet  to,  415 

of  fetus,  table,  389 

food   requirement   during,   chapter, 
379 


Growth 

impulse  of,  in  pigs  and  rats,  368 
influence  of 

accessory  substances  upon,  369 

almond  oil  on,  369 

beef  fat  on  369 

butter  fat  on  369 

calcium  upon,  374,  412 

casein  upon,  370,  376 

cod-liver  oil  on,  369 

cornmeal  upon,  370,  374 

cotton-seed  oil  on,  369 

cystein  on,  377 

edestin  on,  376 

egg  yolk  on,  369 

entire  wheat  kernel  upon,  370 

gliadin  upon,  375 

glutelin  on,  373 

lactalbumin  in,  376 

lard  on,  369 

lysin  upon,  372,  375 

milk  upon,  374,  377 

milk  salts  on,  374 

oats  upon,  370 

olive  oil  on,  369 

organic  phosphorus  on,  371 

proteins,  diverse,  upon,  376 

purified    food-stuffs    upon,    sum- 
mary, 370 

rye  upon,  370 

soy  bean  glycinin  in,  376 

squash-seed  globulin  in,  376 

tryptophan  upon,  372 

various  grains  upon,  370 

water-soluble  vitamins  on,  368 

wheat  proteins  upon,  370,  375 

zein  upon,  372 
law  of,  413 

normal  energy  requirement  in,  415 
rapidity  of,  and  longevity,  416 
in  rats,  capacity  for,  when  lost,  375 
relation  of,  to  ingested  energy,  410, 

411,  413,  414 
retention  of 
v  energy  in,  412 

in  various  animals,  415 

protein  in,  403 
specific  vitamins  for,  367 
studies  on,  368,  369,  370 
of  suckling  pigs,  relation  of,  to  milk 

ingested,  table,  410,  411 
uniform,  tendency  toward,  412 
value  of  various  proteins  in,  table, 

378 
"Growth  quota"  of  protein,  definition, 

276 
Gruber,  163 
Grund,  487 
see  Baumgarten,  483 


6oS 


INDEX 


Guanase 

action  of,  533 

occurrence  of,  533 
Guanido-acetic    acid,    action    of    ar- 

ginase  on,  205 
Guanidin  acetic  acid,  creatin  from,  205 
Guanidin  nucleus  in  amino-acids,  204 
Guanin 

from  guanosin,  529 

structure  of,  527 
Guanosin 

fate  of,  injected,  539 

guanin  from,  529 

from  guanylic  acid,  529 

hydrolysis  of,  529 

d-ribose  from,  529 

xanthosin  from,  530,  531 
Guanylic  acid,  528 

guanosin  from,  529 
hydrolysis  of,  529 
Gudzent,  550 

Guernsey,  see  Eward,  374 
Guion,    C.   M.,  and   Benedict,  S.  R., 

452 


Haas,  164, 190 

Hagemann,  386 

Hahn,  Massen,  Nencki,  and  Pawlow, 

536 
Hair 

of  dog,  nitrogen  excreted  in,  22 
effect  of 

upon    heat    production    in    dog, 

table,  137 
on  metabolism  in  rabbits,  138 
and  heat  loss,  136 
human 

growth  of,  22 
nitrogen  in,  22 
Haldane  and  Priestley,  217 
Haldane,  see  Boycott,  433 

see  Douglas,  427,  430 
Halsey,  195 

Hamalainen  and  Helme,  168 
Hamalainen,  see  Becker,  348 
Hanriot  and  Richet,  86 
Hansen,  see  Henriques,  133,  158 
Hari 
effect  of  blood  plethora  upon  metab- 
olism, 422 
heat  in  protein  hydrolysis,  79 
Hari  and  von  Pesthy,  effect  of  cold 

milk  upon  metabolism,  123 
Harrold,  see  Lee,  324 
Hart  and  Humphrey,  394 
Hart  and  McCollum,  374 
Hart,  see  Steenbock,  219 
Hartogh  and  Schumm,  457 


Hasselbalch 

effect  of 

hydrogen-ion  concentration  of  the 

blood  upon  respiration,  218 
ultra-violet   rays    on    respiration, 

IS°. 
metabolism  of  new-born  infants,  404 

metabolism  during  pregnancy,  384 
respiration   of  eggs  during   incuba- 
tion, 380 
Hasselbalch  and  Lindhard 
effect  of 

sun's  rays  on  respiration,  150 
ultra-violet  rays  of  the  sun  upon 
metabolism,  429 
metabolism   at   low   atmospheric 
pressure,  428 
Hawk,  162 
Hawk  and  Gies,  421 
Hawk,  see  Howe,  71,  104 

see  Sherman,  170 
Heart 
'glucose  utilization  by,  and  hydro- 
gen-ion concentration,  261 
glycogen  in,  during  starvation,  260 
Heart-beat,  reduction  of,  by  low  tem- 
perature, 116 
Heat 
animal 

Depretz's  experiment  on,  34 
Dulong's  experiments  on,  34 
Lavoisier's  experiments  on,  ^ 
of  combustion 

of  carbohydrates,  42 
of  fats,  42 
of  human  feces,  53 
comparison  of  direct  and  indirect, 

in  metabolism,  43 
elimination  in  typhoid  fever,  chart, 
relation  to  heat  production,  508, 

5°9 
extraneous,  and  metabolism  of  foods, 

150 
loss 

by  conduction  and  radiation,  131 

distribution  of,  after  meat  inges- 
tion at  various  and  environ- 
mental temperatures,  table,  235 

and   environmental   temperature, 

protection  against,  136 
by  vaporization  of  water,  131 
and  wind,  145 
manner  of  loss,  131 

at  different  temperatures,  chart, 

141 
and  environmental  temperature, 
table,  140 
mechanical  equivalent  of,  34 


INDEX 


609 


Heat 

from  metabolized  protein  and  fat, 

method  of  calculation,  41 
production  of,  in  fasting,  97 
prostrations,  conditions  for,  148 
regulation  and  clothes,  148,  149 
Rubner's  table  of  direct  and  indirect, 

in  metabolism,  43 
of  sun  and  body  temperature,  149 
value  of  feces,  calculation  of,  54 
of  vaporization  of  water  in  fever,  511 
Heat  production 

and  age  of  children,  407 
in  artificial  anemia,  422 
and  body  temperature  in  fever, 

505,  506,  509 
and  body  weight  in  infants,  chart, 

408 
in  cardiac  diseases,  497 
in  cardiorenal  disease,  497 
cause   of   increase   in,   after   car- 
bohydrate, 297,  298 
in  climbing  Pike's  Peak,  431 
comparison    of,    with    energy    of 

metabolism  in  mountaineering, 

33o  _ 
of  cretin,  table,  442 
of  curarized  dogs  after  protein,  246 
in  diabetes,  473,  474,  475 
effect  of 

agar-agar  upon,  232 

cathartics  upon,  2^2 

feeding  glucose  plus  fat  upon, 
chart,  253 

hair  upon,  in  dog,  table,  137 

urea  ingestion  upon,  231 

water  ingestion  upon,  23 1 
in  egg  during  incubation,  379,  380 
during  emaciation,  406 
and   environmental    temperature, 

table,  137 
in  exophthalmic  goiter,  table,  442 
fasting  in  phosphorus  poisoning, 

491 
in  fundulus  eggs,  3S0 
increase  in,  after  glucose  ingestion, 

290 
increased,  influence  of,  upon  wear 

and     tear     quota     of     protein 

metabolism,  501,  502 
of  an  infant  and  environmental 

temperature,  404 
influence  of 

lactation  upon,  383 

sciatic  and  sympathetic  nerves 
on,  in  curarized  dog,  115 
after  ingestion  of  fat,  251,  252,  253 
in  nephritis,  496 
of  new-born  infant,  3S3 

39 


Heat  production 

in  normal  adult  men,  table,  127 
and    protoplasmic    mass,   experi- 
ment on, 130 
"secondary"  rise  in,  233 
of  silkworm  larvae  during  devel- 
opment, 379 
source  of,  after  fat  ingestion,  254 
summation  of,  during  mechanical 

work,  311,  312 
and  surface  area,  charts,  128,  409 
in  various  resting  animals,  table, 
119,  122 
Hefter,  548 
Heidenhain,  132 
Heijl,  see  Johansson,  289 
Heilner,  162 
Heineman,  319 
Hele,  see  Garrod,  196 
Helle,  Mueller,  Prausnitz,  and  Poda, 

393 
Hellsten,  324,  325 
Helme,  see  Hamalainen,  168 
Helmholtz,  35 
Hemoglobin 
in  anemia,  424 
in  artificial  anemia,  423 
in  carbon  monoxid  poisoning,  434 
composition  of,  in  anemia,  425 
in  fasting,  106 
at  high  altitudes,  435,  436 
from  pyrrolidin  carboxylic  acid,  203 
Hemorrhage,  see  Blood-letting. 
Hemp-seed  oil,  influence  of,  upon  lac- 
tation, 394 
Henderson,  Lawrence  J. 
acid  and   the  base  balance  in  the 

body,  213 
loss  of  optical  activity  of  glucose, 
261 
Henderson,  L.  J.,  and  Palmer 

acid  elimination  in  nephritis,  496 
acid  formation  in  the  organism, 

217 
hydrogen-ion     concentration     of 
urine,  217,  361 
Henderson,  Yandell,  and  Dean,  158 
Henderson,  Yandell,  see  Douglas,  427, 

43° 
Henriques 
gaseous  exchange  in  the  blood,  41 S 
metabolism    of    a    hedge-hog    after 

hibernation,  116 
nitrogen     equilibrium     with     com- 
pletely hydrolyzed  protein,  159 
Henriques  and  Anderson 

nitrogen  retention  after  injection 

of  hydrolyzed  meat,  161 
protein  sparing  by  urea,  284 


6io 


INDEX 


Henriques  and  Hansen 

nitrogen  equilibrium  with  hydro- 

lyzed  casein,  158 
surface   temperature   at   different 
depths  of  a  hog's  back,  133 
Hensel  and  Riesser,  197 
Hepatic  disease 

function  of  carbohydrates  in,  493 
nitrogen  equilibrium  in,  493 
Herbivora,  feces,  50 
Hermann,  49 

Hermanns,  see  Fromherz,  196 
Herring,  200.     See  Simpson,  116 
Herrmann,  see  Begun,  220 
Herxheimer,  358 
Hess,  365 
Heubner,  403,  404 

see  Rubner,  399,  401,  403,  412 
Hexoses,    intermediate    substance    in 

d-lactic  acid  production  from,  264 
Hibernation 

metabolism  during,  table,  116 

pituitary  gland  during,  439 
Hiddings,  see  Murschhauser,  140 
Higgins,  219 
Higgins  and  Means,  553 
Higley  and  Bowen,  325 
Hilditch,  see  Mendel,  545 

see  Underhill,  444 
Hill  and  Flack,  419 
Hindhede 

low  protein  dietary,  340 

nitrogen  balance  after  various  forms 
of  bread,  341 

utilization  of  potato  protein,  341 
Hippuric  acid 

elimination  of,  185 
formation  of,  182,  185 
Hirsch,  Mueller,  and  Roily,  503 
Hirsch  and  Reinbach,  449 
Hirschfeld,  342 
Hirz,  491 
His,  550 
Histidin 

diazo  reaction  of,  205 

fate  of,  205 

glucose  from,  205 

occurrence,  205 

/3-oxybutyric  acid  from,  205 

and  urochrom,  205 
Hoagland,  see  McCollum,  187 
von  Hoesslin,  515 
Hoffmann,  see  Boehm,  449 
Hoffstroem,  389 
Hofmeister 

"accessary  food-stuffs,"  363 

alimentary  glycosuria  in  the  fasting 
organism,  447 

structure  of  protein  molecule,  175 


Hogan,  374 

Hoist,  365 

Hoist  and  Froelich,  364 

Homans,  488 

Homer,  206 

Homogentisic  acid 

aceton  bodies  from,  197 
formation  of,  196 
origin  of,  in  alcaptonuria,  195,  196 
from  para  -  oxy  -  phenyl  -  pyruvic 

acid,  178 
from  phenyl-alanin,  178,  195,  196 
from  tyrosin,  178,  195,  196 

Honjio,  190 

Hoobler,  245 
see  Murlin,  407 

Van  Hoogenhuyze  and  Verploegh,  210, 

Hopkins,  F.  G. 

accessory  factors  of  diet,  363 
growth  with  a  synthetic  food,  368 
relation  of  growth  to  energy  of  diet, 

414 
see  Fletcher,  420 
see  Willcock,  372 
Hopkins  and  Cole] 

isolation  of  tryptophan,  206 
Horbaczewski,  531 
"Hormones" 

"exogenous,"  378 
"food,"  378 
Hornemann,  358 
Hospital,  dietaries,  table,  351 
Howe  and  Hawk,  104 
Howe,  Mattill,  and  Hawk,  71 
Howell,  79 
Howland 
calorimetric   observations  upon   in- 
fants, 405 
metabolism  of  the  sleeping  infant, 
122 
Howland  and  Marriott 

acidosis  in  infants,  497 

ammonia     excretion     after     acid 

phosphate  ingestion,  222 
effect  of  hydrochloric  acid  in  diet, 
220 
Humidity 

and     environmental     temperatures, 
effect    upon    body    temperature, 
table,  147 
and  metabolism,  139,  140 
and    temperature,    influence    upon 
metabolism,  table,  147 
Humphrey,  see  Hart,  394 
Hunger 

appetite  as  expression  of,  107 
calcium,  definition  of,  69 
definition  of,  69 


INDEX 


6ll 


Hunger 

knee-jerk  in,  71 
movements  of  stomach  in,  70 
pangs,  inhibition  of,  71 
protein,  definition  of,  69 
specific  nitrogen 
cases  of,  274 
definition  of,  274 
water 

definition  of,  69 
fatality  of,  70 
Hunter  and  Givens 

allantoin  excretion  of  the  coyote, 

536 
excretion  of  purin  bases,  536 
purin  content  of  urine  of  various 
species  of  animals,  537 
Hunter,  Givens,  and  Lewis 

metabolism  in  pellagra,  367 
Hydrazin,  effect  of,  on  metabolism,  494 
Hydrochloric  acid,  219 
Hydrogen-ion 

concentration  of  blood,  214,  215 
in  acidosis,  468 

of  infants,  498 
in  diabetes,  table,  468 
in  neurogenic  fever,  504 
concentration  of  urine,  217 
on  mixed  diet,  361 
from  vegetarians,  361 
explanation  of,  214 
exponent,  215 
Hyperthermia,  499 
Hyperthyroidism,  442,  443 
Hypophysis,  affections  of,  carbohydrate 

tolerance  in,  439 
Hypopituitarism,  438 
Hypoxanthin 
fate  of,  when  ingested,  532 
structure  of,  527 


Ibrahim,  258 

see  Soetbeer,  538 
Iceland  moss,  nutritive  value  of,  54 
Ichthyosis  hystrix,  metabolism  in,  at 

high  temperature,  500,  501 
Imbrie,  490 
"Improvement     quota"     of     protein, 

definition  of,  276 
Inagaki,  see  Schwenkenbecker,  511 
Inanition,  see  Fasting. 
Indol 

excretion  of,  207 

from  tryptophan,  206 
Infant  feeding,  400 
Infants 

acidosis  in,  497 

treatment  of,  table,  498 


Infants 

calorimetry,     direct    and    indirect, 
correspondence     between,     table, 

405 
crying,  energy  expended  by,  407 
maintenance  minimum  of,  404 
metabolism  of,  122,  401,  402 
new-born,  383 
prematurely    born,    metabolism   of, 

39? 

relation  of  heat  production  to  body 
weight,  chart,  408 
to  surface  area,  chart,  409 
Inosin,  from  adenosin,  530,  531 
Internal  secretions,  influence  of,  upon 

metabolism,  438,  439,  440 
Intoxication,  alcohol  in  blood  during, 

356, 357 
Inulin,  nutritive  value  of,  54 
Iron 

in  American  dietaries,  360 

daily  requirement  of,  359 

in  milk,  398 

retention     of,     at     high     altitudes, 

435 
Irreducible  minimum  of  protein  "wear 

and  tear"  quota,  282 
Isaac,  259 
Ishimori,  259,  446 
Iso-dynamic  law,  36 


Jackson,  45S 

Jackson  and  Blackfan,  549 
see  Mandel,  4S6 
see  Mendel,  206 
Jacobs,  see  Levene,  528,  529 
Jacoby,  492 
Jaegeroos,  386 
Jaffa,  343 
Jaffe,  107,  204 
von  Jaksch 

carbohydrates    in    phosphorus    poi- 
soning, 493 
purin  excretion  in  tuberculosis,  523 
use  of  pentoses  in  diabetes,  488 
Janeway  and  Oertel,  488 
Janney 
excretion  of  ammonia  after  sodium 

bicarbonate  ingestion,  222 
"extra"  sugar  in  urine  after  meat 

ingestion,  243 
nitrogen    and    glucose    elimination 
after  ingestion  of  serum  albumin, 
225 
urea  and  ammonia  formation,  165 
Janney  and  Blatherwick 
quantities  of  glucose  from  various 
forms  of  protein,  172,  456,  457 


6l2 


INDEX 


Janney   and    Csonka,    calculation    of 

D  :  N  ratio,  456 
Janney,  see  Dakin,  192,  208 
Jaquet,  425 
Jensen,  260 

Jochmann,  see  Traube,  501 
Johansson 

carbon  dioxid  excretion  after  glucose, 
290 

chemical  regulation  of  temperature, 

i43 
"Darmarbeit,"  232 
influence    of   fatigue    upon    metab- 
olism, 322 
night  and  day  metabolism,  no 
regularity  of  temperature  and  met- 
abolism, 113 
Johansson,  Billstrom,  and  Heijl 

carbon  dioxid  elimination  after 
cane  sugar  ingestion,  289 
Johansson  and  Koraen 

carbon  dioxid  elimination  in  me- 
chanical work,  325 
Johansson,  Landergren,  Sonden,  and 
Tigerstedt 
fecal    production    in  fasting, 

metabolism  of  J.  A.  in  star- 
vation, 87 
Jolles  and  Friedjung,  398 
Jonas,  see  Ringer,  201,  202,  203 
Jones,  D.  B.,  see  Osborne,  77,  78 
Jones,  Walter 
nucleic  acids,  527 

scheme  of  methods  of  breakdown  of 
guanin-adenin  dinucleotid,  530 
Jones  and  Austrian 

guanase,    adenase,    and    xanthin 

oxidase  in  cattle  livers,  533 
guanase  in  organs  of  pig,  534 
Jones  and  Partridge 

guanase  and  adenase  in  organs  of 

pi?-r,  533 
Jones  and  Richards 

action  of  nucleinase,  530 
Jones,  see  Amberg,  530 

see  Miller,  549 
Jones,  W.  S.,  see  Carlson,  453 
Jordan  and  Jenter,  393 
Joslin 
Allen  treatment  of  diabetes,  481 
respiratory    quotients    in    diabetes, 

480,  483 
treatment  of  diabetes  in  pregnancy, 

483 
see  Benedict,  F.  G.,  295,  474 
Joule,  34 
Jundell,  417 
Junkersdorf,  see  Pflueger,  175 


KALBERLAH,  see  Embden,  264 
Karsner,  see  Fiske,  221 
Katz,  98 

Katzenstein,  326,  330 
Kauffmann,  157 

Kautzsch,  see  Abderhalden,  202 
i  Kemmerich,  391 
Kermauner,  52 
"Keto-aldehyd  mutase,"  193 
Keto-glutaric  acid,  succinic  acid  from, 

202 
Keto-succinic  acid,  pyruvic  acid  from, 

201 
Kidney 

efficiency  of,  table,  166 

urine    volume    and    nitrogen    from 
each,  165 
Kidney  tissue 
action  upon 

d-fructose,  264 
d-glucose,  264 
d-mannose,  264 
Kiesel,  397 
Kinberg,  275 
King,  see  Barcroft,  433 
Kirchmann,  156 
Klein  and  Moritz,  222 
Kleiner  and  Meltzer,  450 
Klemperer,  523 

see  von  Leyden,  520 
Klemperer,  and  Umber  490 
Knaffl-Lenz  and  Wiechowski,  550 
Knee-jerk,  in  hunger,  71 
Knoop,  182,  285 
Kober,  see  Levene,  176 
Koch  and  Voegtlin,  367 
Koch,  Elizabeth,  351 
Kocher 

protein  metabolism  during  walking, 

317,  So2 
toxic  destruction  of  protein  in  fever, 

5i3 
Koehler,  423 
Kolb,  see  Elias,  447 
Kolmer,  see  Brezina,  323 
Kondo,  264,  490 
Koraen,  see  Johansson,  325 
Korkunoff,  see  E.  Voit,  153,  254,  277 
Kossel 
amino-acid  production  in  fasting  in 

salmon,  82 
composition  of  protein  molecule,  175 
hydrolytic  cleavage  products  of  nu- 
cleic acid,  527 
purins  in  incubated  egg,  539 
relation  of  glucose  to  protein  end- 
products,  172 
Kossel  and  Dakin 

enzyme  splitting  d-arginin,  203 


INDEX 


613 


Kossel  and  Steudel 

pvrimidin  nucleus  of  purin  bases, 
528 
Kossow,  see  Fischler,  466 
Kotake,  182 

Kramer,  see  Murlin,  473,  474,  485 
Kramsztyk,  see  Michaelis,  217 
Kraske,  264 
Kraus,  517 

Krause,  see  Cramer,  442 
Krehl 

cause  of  continuance  of  fever  when 

heat  elimination  is  increased,  510 
Krehl  and  Matthes 

albumoses  in  urine  during  fever, 

523 
Kriwuscha,  see  Szalagyi,  541 
Krogh 

metabolism  of  normal  frog,  114 
of  fish  and  curarized  dog,  115 
Krogh  and  Krogh 

relation  of  carbon  dioxid  tension 
in  alveoli  and  arterial  blood,  217 
Krueger  and  Schmidt,  532 
Krummacher,  157,  315 
Kuelz 

effect   of   tetanus   on   glycogen     in 

organism,  107 
glycogen  in  the  heart  during  star- 
vation, 260 
origin  of  glycogen  from  proteint  171 
Kumagawa,  105 
Kumagawa  and  Miura,  71 
Kuenzel  and  Schittenhelm,  534 
Kynurenic  acid 

and  gelatin  metabolism,  206 
and  protein  metabolism,  206 
from  tryptophan,  81,  205,  206 


Laborer 

Atwater's  protein  ration  for,  335,  336 
Italian,  protein  in  dietary  of,  335 
Rubner's  protein  ration  for,  335,  336 
Voit's  protein  ration  for,  335,  336 
Lactacidogen  theory,  264 
Lactalbumin,  comparative  value  of,  in 

growth,  376 
Lactation 
influence  of 

diet  during,  391 
on  heat  production,  383 
hemp-seed  oil  upon,  394 
Lactic  acid 

from  alanin,  191 
in  blood,  263 

in  high  altitudes,  433 
after    moderate    exercise,    ex- 
planation of,  322,  323 


Lactic  acid 

effect  of,  in  body,  493 

from  fructose,  264 

glucose  from,  191,  262 

from  glucose,  263 

from  glyceric  acid,  262 

from  glycogen,  263 

from    methyl-glyoxal,     192,    193, 

264,  265 
in   muscle   under  anaerobic   con- 
ditions, 420 
after  muscle  damage,  264 
in  normal  muscle,  263 
origin  of  the  methyl  group,  193 
oxidation  of,  266 

in  phosphorus  poisoning,  263,  493 
from  pyruvic  acid,  180,  181 
in  rigor  mortis,  263 
significance  of,  491 
and  specific  dynamic  action,  245, 

246 
from  trioses,  265 
urinary 

in  anemia,  421,  422 
in  asphyxia,  266 
in  oxygen  lack,  427 
Lactose 

replacement    of    fat    by,    in   infant 

feeding,  412 
oxidation,  294 
in  urine,  396 
La  Forge,  see  Levene,  487 
Lampe,  see  Abderhalden,  96 
Lamson,  see  Turner,  82 
Landau, 545 
Landergren 

influence    of    previous    protein    in- 
gestion  upon   nitrogen   excretion 
with  fat  and  carbohydrate  diet, 
275,  281 
protein  metabolism  in  fasting,  273 
protein    sparing    by    carbohydrate, 

2  73 

see  Johansson,  51,  87,  90 
Lang,  511 

Langley  and  Edkins,  105 
Langstein  and  Meyer,  196 
Langstein,  see  Abderhalden,  400 

see  Neuberg,  191 

see  Rubner,  390 
Laplace,  18 

see  Lavoisier,  ^^ 
Lard 

influence  of,  on  growth,  369 

respiratory  quotient  from,  59 
Larvae,     silkworm,     heat     production 

during  development  of,  379 
Lauder  and  Fagan,  395 
Lavoisier,  18 


614 


INDEX 


Lavoisier  and  Laplace,  33 
Lavonius,  331,  346 
Law 

Ambard's,  165 

of  conservation  of  energy,  confirma- 
tion of,  43,  320 
of  energy  expenditure,  413 
Fleurens',  of  longevity,  table,  416 
of  growth,  413 
the  iso-dynamic,  36 
Newton's,  123 
of  surface  area,  119,  383,  406,  475, 

554 
comparison  in  different  animals, 

.4I 
discovery  of,  41 

Lead  poisoning,  uric  acid  in  blood  in, 

547 
Leathes,  524 

Leavenworth,  see  Osborne,  77 
Lee 

influence   of   temperatures   and  hu- 
midities   on   body    temperatures, 

147 . 
on  fatigue,  430 

Lee  and  Harrold 

fatigue  in  phlorhizin  diabetes,  324 
Lefevre,  143,  506 
Lefmann,  212 

Lehmann,    Mueller,    Munk,    Senator, 
and  Zuntz 
production  of  feces  in  fasting,  451 
respiratory  quotient  of  lard,  59 
Lehmann,  C,  and  E.  Voit 

fat  from  carbohydrate,  305 
Lehmann  and  Zuntz 

importance   of   muscular   rest   in 

metabolic  experiments,  no 
metabolism  of  Cetti  in  starvation, 
86 
Lemaire,  396 
Leschke,  see  Citron,  510 
Lesser,  420 
Leucin 

fate  of,  195 
glucose  from,  195 
occurrence,  195 
/3-oxybutyric  acid  from,  195 
Leukemia,  424 

excretion  of  uric  acid  in,  547 
lymphatic 

effect  of  x-ray  therapy  in,  425 
metabolism  in,  425 
Leukocytes 
action  of 

upon  d-galactose,  264 
upon  d-glucose,  264 
upon  d-mannose,  264 
on  pyruvic  acid,  192 


Levene 

effect  of  leukocytes  and  kidney  upon 

amino-acids,  176 
glucose  in  bile  after  phlorhizin,  451 
on  guanase  and  adenase,  533 
Levene  and  Jacobs 

formula  for  nucleic  acid,  529 
guanylic  acid  and  nucleic  acid,  528 
Levene  and  Kober 

urea    excretion    after   amino-acid 
ingestion,  176 
Levene  and  La  Forge 

pentose  in  pancreas  and  liver,  487 
d-ribose  in  urine  in  pentosuria,  487 
Levene  and  Medigreceanu 

ferment  cleavage  of  nucleic  acid, 

529 
Levene  and  Meyer 

effect   of   leukocytes   and   kidney 

tissue  on  pyruvic  acid.  192,  267 

glycolysis  induced  by  leukocytes, 

264 
lactic  acid  from 

methylglyoxal  by  white  blood 

cells,  265 
sugars  by  leukocytes  and  kid- 
ney tissue,  264 
urea  excretion  after  gylcyl-glycin, 
176 
Levinthal,  532,  538 
Levulose,  see  Fructose. 
Levulosuria,  a  case  of,  486 
Levy,  Rowntree,  and  Marriott,  219 
Lewinski,  106,  185 
Lewinstein,  423 
Lewis,  H.  B.,  185,  187 
Lewis,  H.  B.,  see  Taylor,  81,  83 
Lewis,    R.    C,   see    Benedict,    S.    R., 

455 

see  Hunter,  367 

see  Mendel,  169 
von  Leyden 

metabolism  in  fever,  506 

water 

retention  in  fever,  522 
vaporization  in  fever,  511 
von  Leyden  and  Klemperer 

metabolism  in  pneumonia,  520 
Lichtenfelt,  335,  341 
Liebermeister,  511 
Liebig 

origin  of  organic  analysis,  20 

oxidations  in  the  body,  19 

training  of,  18 
Life,  length  of,  in  various  animals  in 

starvation,  table,  103 
Lindemann  and  May,  488 
Lindhard,  150 

see  Hasselbalch,  150,  428,  429 


INDEX 


615 


Linear  formula 

for  surface  area,  125 
validity  of,  table,  129 
Linseed  oil,  influence  of,   upon  milk 

fat,  394 
Linser,  549 

Linser  and  Schmid,  500 
Lipemia,  in  diabetes,  490 
Lissauer,  54 
Litten,  521 
Liver 

amino-acids    in,    after    phosphorus 

poisoning,  492 
carcinoma  of,  and  creatin  in  urine, 

212 
fat 

during  starvation,  249 
influence  of   carbohydrate   upon, 
249 
glycogen  of,  258 

in  depancreatized  dogs,  448 
and    muscle,    relation    of    absorbed 

amino-acids,  81 
retention  of  amino-acids  in,  80 
urea  formation  by,  222 
1-xylose  from,  487 
LoerHer,  464 
Loewi 

colloidal  sugar  in  blood,  451 
nitrogen    equilibrium    with    protein 

cleavage  products,  157 
uric    acid    excretion    after    nucleo- 
protein  ingestion,  538 
Loewy 

heat  value  of  respiratory  gases  in 

metabolism,  62 
loss  of  water  of  perspiration,   131, 

minimum  metabolism  of  man,  no 
muscular  exercise   and   protein   re- 
tention, 317 
respiratory  quotient  for  protein,  60 
Loewy  and  Muenzer 

blood  C02  after  hydrochloric  acid 
ingestion,  219 
Loewy  and  Zuntz 

oxygen  absorption  by  hemoglobin, 

434 
respiratory    metabolism    at    low 

pressures,  428 
saturation  of  hemoglobin,  432 
Loewy,  see  Caspari,  433 

see  Zuntz,  333,  435 
Lohrisch,  54 

London  and  Boljarski,  210 
London,  see  Abderhalden,  81,  536 
Longevity,    Flourens'    law    of,    table, 

416 
Lossen,  31 


Luciani 

bod}'  temperature  of  Succi  during 

fasting,  in 
fasting,  71 
Succi's  gastric  juice  during  fasting, 

io5 
Succi's    nitrogen    excretion    during 

fasting,  90,  91 

Ludwig,  19 

Luethje 

castration  upon  metabolism,  438 

nitrogen     retention     after     copious 
nitrogen  ingestion,  286 

P2O5  retention  in  convalescents,  286 

sugar  from  protein,  456 
Lukacs,  see  Mansfield,  115 
Lumbermen 

Maine,  dietary  of,  348 

metabolism  of,  320 

protein  in  dietary  of,  336 
Lungs 

area    decreased,    metabolism    after, 

425 
blood  capillaries  of  area  of,  418 
emphysema  of,  gaseous  exchange  in, 

425 
impermeability  to  ammonia  of,  22 
ventilation  of,  at  different  altitudes, 
table,  431 
Lusk 
cause  of  rise  in  heat  production  after 

glucose  ingestion,  294 
creatinin  elimination  in  phosphorus 

poisoning,  210 
diabetes  and  protein  metabolism,  463 
D  :  N  after  phlorhizin,  455 
experiments  on  Rubner's  theories  of 

specific  dynamic  action,  240 
extra  sugar  in  urine  in  diabetes 
after  cold,  457 
after  tetanus,  107 
after  work,  457 
gelatin  as  protein  sparer,  282 
glucose  from 

amino-acids,  208 
glutamic  acid,  201 
glycogen  from  fructose,  258 
glycosuria    after    phlorhizin    injec- 
tions, 450 
heat  production 

after  amino-acid  ingestion,  243, 

298 
after  cold  baths,  144 
after  ingestion  of  cold  foods,  123 
in  diabetes,  474 
after  fat  ingestion,  252 
after  glucose  ingestion,  307 
after   glycocoll   ingestion,    244, 
245>  295 


6i6 


INDEX 


Lusk 

heat  production 

after  phlorhizin  injection,  474 
in  phosphorus  poisoning,  491 
after  urea  ingestion,  231 

milk  secretion  in  starving  goats,  106, 

392        .  . 

non-protein  respiratory  quotient  in 

severe  diabetes,  471 
phloretin,  324 
phlorhizin  glycosuria,  99,  188,  450, 

455 
on  protein  in  dietary,  343 
protein  metabolism 

after  epinephrin,  460 
after    withdrawal    of   carbohy- 
drate,-269 
respiratory   quotient   of   protein   in 

diabetes,  470 
stimulation     of     metabolism     after 

amino-acid  ingestion,  412 
thyroid,  influence  of,  440,  460 
Lusk  and  McCrudden 

heat  production  per  square  meter 
of  body  surface  in  dogs  and  a 
dwarf,  122 
Lusk,  Graham 

see  Benedict,  F.  G.,  358 

see  Gephart,  563 

see  Mandel,  191,  262,  455,  457,  462, 

490 
see  Murlin,  63,  252,  296,  298 
see  Parker,  186 
see  Ray,  492 

see  Reilly,  107,  156,  172,  455,  463 
see  Ringer,  188,  191,  193,  197,  198, 

200 
see  Stiles,  99,  172,  451,  455 
see  Williams,  224 
Lusk,  W.  T.,  400 
Luzzatto,  487 
Lyman,  see  Mendel,  534 
Lysin 

cadaverin  from,  203 

fate  of,  203 

influence  of,  upon  growth,  372,  375 


Macallum,  A.  Bruce,  see  Funk,  414 

MacCallum,  444 

Macleod,  447 

Magnesium  and  nitrogen  ratio  during 

fasting,  98 
Magnus,  19,  22, 
Magnus-Levy 

acetaldehyd  as  cleavage  product  of 
carbohydrate,  267 

aceton  bodies,  464,  469 

benzoylated  amino-acids,  186 


Magnus-Levy 
carbon  dioxid  in  blood,  467 
diabetes,    respiratory   quotients   in, 

47o, 47i  . 
glycosuria   in   exophthalmic   goiter, 

459 
heat  production  in  emaciation,  476 
hippuric  acid  excretion  after  sodium 

benzoate  ingestion,  186 
influence  of 

fat    ingestion    upon    metabolism, 

nucleo-protein  ingestion  upon  uric 
acid  excretion  in  gout,  547 
metabolism 

in  acromegaly,  439 
in  anemia,  424 
after  cane  sugar,  289 
in  carcinoma,  512 
in  diabetes,  469 
in  exophthalmic  goiter,  441 
in  gout,  544 

after  meat  ingestion,  247 
in  pregnancy,  547 
after  thyroid  ingestion,  440 
uric  acid  excretion  and  gout,  547 
Magoon,  see  McClendon,  215 
Maintenance  minimum  of  infants,  404 
Maize,  nutritive  value  of,  373 
Malic  acid,  glucose  from,  201 
Mandel 
body  temperature  of  monkeys  after 

xanthin,  524 
purin    bases    and    temperature    in 
aseptic  fever,  523 
Mandel  and  Jackson 

glucuronic    acid    excretion    after 
camphor  ingestion,  486 
Mandel  and  Lusk 

colloidal  glucose  in  blood,  462 
D  :  N  in  human  diabetes,  455 
glucose  from  d-lactic  acid,  191,  262 
lactic  acid  in  phosphorus  poison- 
ing after  phlorhizin  injections, 
490 
Mandelic  acid  from  phenyl-glycocoll, 

177 
d-Mannose 

kidney  tissue  upon,  264 
leukocytes  upon,  264 
from  glucose,  260 
Mansfeld,  440 
Mansfield  and  Lukacs,  115 
Mansfield,  see  'Woods,  320,  336,  348 
Marchand,  see  Erdmann,  183 

see  Freund,  145,  447,  457 
Marching,  economy  in,  331 
Marriott 
aceton  bodies  in  blood,  250,  466,  467 


INDEX 


617 


Marriott    and     Wolf,    artificial     cys- 

tinuria,  199 
Marriott,  see  Howland,  220,  222,  497 

see  Levy,  219 
Marsh,  see  Meigs,  400 
Marshall  and  Davis,  165 
Marshall,  see  Turner,  82 
Masing,  269 
Mass 

protoplasmic,  and 
heat  production, 
experiment  on,  123,  130 
Mass    action    and     specific    dynamic 

action,  246 
Massen,  see  Hahn,  536 
Mathews  and  Nelson,  81 
Matsuoka,  see  Ellinger,  206 
Matthes,  see  Krehl,  523 
Mattill,  see  Howe,  71 
Maximal    economic    velocity,    defini- 
tion of,  328 
May,  504.  512 

see  Lindemann,  488 
Mayer,  J.  R.,  34 
Mayer,  P. 

cleavage  products  of  aspartic  acid 
metabolism,  201 

glucose  from  glycol  aldehyd,  190 

lactic  acid  from  pyruvic  acid,  181 
Mayer,  see  Armand-Delille,  2S5 
Mayow,  18 

McClendon  and  Magoon,  215 
McCollum 

on  growth  impulse,  367 

influence  of 

organic  phosphorus  upon  growth, 

purified  food-stuffs  upon  growth, 

37° 

sodium  benzoate  on  protein  met- 
abolism, 286 
nitrogen  retention  after  low  nitro- 
gen diet,  287 
protein  sparing  by  gelatin,  283,  373 
starch  and  inorganic  salts  as  sole  diet 

for  pigs,  209 
vitamin  terminology,  363 
McCollum  and  Davis 

butter  fat  upon  growth,  369 
dialyzed     casein     upon    growth, 

37o 
grains  upon  growth,  370 
vegetable  oils  upon  growth,  369 
McCollum  and  Hoagland,  187 
McCollum,  see  Hart,  374 
McCrudden,  see  Lusk,  122 
McDermott,  see  Ray,  492 
McLean 
constant  for  urea  elimination,  166 


McLean 

elimination  of  sodium  chlorid,  167, 

5-^3 
urea  in  blood  in  nephritis,  495 
McLean  and  Selling 

Ambard's  coefficient,  166 
Means 
acidosis  in  obesity,  94 
metabolism  in  hypopituitarism,  438 
normal  controls,  127 
Means  and  Aub 

.v-ray  therapy  in  lymphatic  leuke- 
mia, 425 
Means,  Aub,  and  Du  Bcis 

metabolism  after  caffein,  554 
Means,  see  Denis,  549 
see  Higgins,  553 
see  Palmer,  211 
Measles,  urine  in,  524 
Meat,  see  Protein. 

excessive  ingestion,  224,  247 
feces  from,  49 
metabolism  of 
in  diabetes.  456 
hourly,  223,  247 
and  temperature  of  environment, 

235 
and  uric  acid  excretion,  543 
nitrogen  excretion 
hourly,  164 
subsequent  to  meat  in  excess, 

73)  275 
phosphate  excretion,  167 
as  sole  diet,  156 
sulphur  excretion,  167    * 
Meat  extract,  26,  231 
Medigreceanu,  see  Levene,  529 
Meeh 

formula  of.  119 
surface  area  formula,  118 
Meigs  and  Marsh,  400 
Meissl  and  Strohmer,  304 
Mellanby 
creatin 
excretion 

in  carcinoma  of  the  liver,  212 
after  Cesarean  section,  212 
in  muscle  during  fatigue,  213 
Meltzer,  S.  J.,  see  Benedict,  F.  G.,  358 

see  Kleiner,  450 
Men 
energy  requirements  of,  in  various 

occupations,  349 
old,  food  needed  by,  351 
Mendel 
food  value 

of     Iceland     moss,     agar-agar, 

artichokes  and  inulin,  54 
of  proteins  of  mushrooms,  54 


6i8 


INDEX 


Mendel 

influence  of 

alanin  upon  growth,  412 
purified  food-stuffs  upon  growth, 

37°. 
protein   in   diet   and    bodily   vigor, 

337 
value  of  various  proteins  in  growth, 

377 
Mendel  and  Brown 

uric  acid  excretion  after  ingestion 
of  meat,  543 
Mendel  and  Hilditch 

influence  of  alcohol  on  purin  ex- 
cretion, 545 
Mendel  and  Jackson 

kynurenic    acid    elimination    and 
protein  metabolism,  206 
Mendel  and  Lewis 

nitrogen  elimination  after  inges- 
tion of  egg  white,  169 
Mendel  and  Lyman 

purin  bases  in  pig  urine,  534 
Mendel  and  Mitchell 

enzymes  in  liver  of  pig,  534 
Mendel  and  Myers 

fate  of  pyrimidin  bases,  528 
Mendel  and  Rockwood 

protein  metabolism  after  injection 
of  edestin,  161 
Mendel  and  Rose 

creatin    oxidation    and    carbohy- 
drate metabolism,  212 
Mendel  and  White 

allantoin  elimination  after  urate 
injection,  535 
Mendel,  see  Osborne,  55,  77,  362,  368, 

369,  372,  373,  375,  376 
Mendelson,  509 
Menstruation 

metabolism  during,  381 
Mercapturic  acid,  formation  of,  199 
von  Mering 

glycosuria    after    phlorhizin    injec- 
tions, 450 
von  Mering  and  Minkowski 

pancreatic  glycosuria,  446,  453 
von  Mering  and  Zuntz 
"Darmarbeit,"  231 
Metabolism 
of  achondroplastic  dwarf  after  meat, 

247 
of  alcohol,  table,  356 
after  amino-acids,  chart,  241 
amino-acid 

C02  cleavage  in,  179 
story  of,  184 
of  anaerobic  frog,  420 
in  anemia,  chapter,  418 


Metabolism 

in    anemia,     calorimetric    observa- 
tions, table,  424 
in  artiiicial  anemia,  421 
in  artificial  blood  plethora,  422 
and  atmospheric  pressure,  428 
during  balloon  ascensions,  428 
basal,  table,  125,  129 
in  acromegaly,  439 
action  of 

amino-acid      stimulation 


on, 


303 


carbohydrate  plethora  on,  302 
fat  plethora  on,  301 
food  upon,  301 

in  anemia,  424 

atropin  upon,  553 

of  boys,  129,  559 

caffein  upon,  553 

camphor  upon,  553 

in  cardiac  disease,  495,  554 

chart  for,  at  various  ages,  1 28 

in  controls,  127 

and  creatinin  elimination,  211 

in  cretinism,  442 

definition,  141,  301 

in  diabetes,  475 

in  exophthalmic  goiter,  441 

increase  in,  after  severe  muscular 
work,  322 

modifications  of,  141 

and  protoplasmic  mass,  211 

strychnin  upon,  553 

in  typhoid  fever,  table,  518 
during  bicycle  riding,  320,  321 
after  blood  letting,  421 
of  boys,  129,  559 
carbohydrate,  294 

acid  production  in,  296,  299 

dynamic  aspects  of,  302 
in  cardiac  disease,  chapter,  495 
after  castration,  438 
of  Cetti  in  starvation,  table,  87 
of  children,  401 
in  chlorosis,  424 
climatic  influences  on,  150 
during   climbing   of   the    Faulhorn, 

table,  315 
clothes  upon,  149,  313 
cold  baths,  influence  of,  table,  144 
cold  food,  influence  of,  table,  123 
of  cretin,  calorimetric  observations, 

table,  442 
of  cystein,  200 
in  decreased  lung  area,  425 
definition  of,  20 
depressed,  example  of,  443 
during  descent,  330 
in  diabetes,  chapter,  445 


INDEX 


619 


Metabolism 

of  diabetic  patient  while  fasting, 
table,  481 

of  differently  conditioned  children, 
table,  401,  402 

in  dog  after  glucose,  table  (quo- 
tients above  unity),  307 

in  dyspnea,  423 

in  dystrophia  adiposogenitalis,  438 

in  emaciation,  476 

energy 

of  children,  407 

of,  comparison  with  heat  produc- 
tion in  mountaineering,  330 

and  environmental  temperature, 
table,  137 

in     exophthalmic    goiter,    chapter, 
418 
calorimetric  observations,  table, 
441,  442 

fast 

data  of  31-days',  96 
in  man,  influence  of  temperature, 
142 

fat 

dynamic  aspects  of,  251,  302 
subcutaneous,  effect  of,  138 

of  a  fat  individual,  effect  of  work 
and  climatic  conditions  upon, 
table,  314 

after  fatigue,  322 

in  fever,  chapter,  490 

increase  of  experiments  on  cause 

of,  501,  520 
induced    by   surra    trypanosoma, 
table,  504,  505 

gelatin,  281 

of  glucose,  as  compared  with  fruc- 
tose, 294,  302 

of  glycocoll 

with  glucose  and  fat,  299 
in  phlorhizin  diabetes,  244 

glycogen,  72,  89 

in  gout,  544 

hair,  influence  upon,  136,  138 

at  high  altitudes,  chapter,  418,  429, 

431-  437,  43.8 

on  summit  of  Monte  Rosa  and 

Col  d'Olen,  429 
during  work,  429 
hourly  increase  in.  after  meat,  223, 

247 
and  humidity,  139,  140 
hydrazin  on,  494 
hypopitutarism  with  accompanying 

obesity,  438 
in  ichthyosis  hystrix,  effect  of  high 
environmental  temperature  upon, 


Metabolism 
increase 

after  cane  sugar  feeding,  duration 

of,  289 
in  carcinoma,  512 
in  diabetes,  acidosis  as  cause  of, 

475 
after  hard  work,  cause  of,  322 
during  speed,  329,  330 

of  an  infant,  table,  402 

intermediary,  of  carbohydrate,  chap- 
ter, 258,  260,  307 

internal  secretions  on,  438 

of  J.  A.  in  starvation,  table,  88 

and  kynurenic  acid,  206 

in  leukemia,  424 
lymphatic,  425 

of  lumbermen,  320 

during  menstruation,  381 

mineral,  of  growing  children,  table, 

417 

minimum,  no 

in  myxedema,  chapter,  418,  443 

in  nephritis,  chapter,  495,  496 

nitrogen 

of  different  animals  in  starvation, 

table,  86 
influence  of  work  upon,  of  fasting 

dogs,  table,  108 
of  Succi  during  work,  109 

normal,  cystin  in,  199 

of  a  normal  and  diabetic  man,  com- 
parison of,  table,  473 

obese  and  thin,  comparison  of,  table, 
256,_  257 

osmosis  upon,  293 

and  oxygen,  pure,  419 

before  and  after  parturition,  382 

in  pernicious  anemia,  424 

in  phlorhizin  glycosuria  after  thy- 
roidectomy, 460,  461 

in   phosphorus   poisoning,    chapter, 

445 
of  pigeon  without  feathers,  138 
posture  upon,  331 

during  pregnancy  in  dogs,  table,  385 
of  prematurely  born  infants,  390 
protein 

and  amino-acids,  78,  79 

in  anaphylaxis,  161 

in  artificial  anemia,  421 

character    of,     during    muscular 
work,  table,  316,  317 

before  and  after  childbirth,  table, 
388  _ 

conditions  of,  288 

deposit  and,  245 

in  diabetes,  influence  of  thyroid 
on,  460 


620 


INDEX 


Metabolism 
protein 

and  diminished  atmospheric  pres- 
sure, 427 
effect  of 

fat   upon,  in  starvation,  table, 

100,  101,  103 
partial   replacement    of    carbo- 
hydrate by  fat  upon,  270 
endogenous,  209 

ammonium  acetate  as  sparer  of, 

283  _ 

ammonium  chlorid  as  sparer  of, 

284  . 

ammonium  citrate  as  sparer  of, 

283 
gelatin  as  sparer  of,  283 
urea  as  sparer  of,  284 

excess  of,  223 

exogenous,  209 

in  fever,  action  of  protein  and  car- 
bohydrate ingesta  on,  501 

glvcocoll  stage  of,  188 

indexed  by  nitrogen  elimination, 
167 

influence  of 

carbohydrate  on,  table,  269,  270 
diabetes  upon,  table,  463 
fat  upon,  248 

intermediary,  chapter,  171 

and  kynurenic  acid,  206 

loss  of  body  weight  in  exclusive, 
102 

lower  limit  of,  compatible  with 
life,  282 

-in  man,  effect  of  high  environ- 
mental temperature  upon,  table, 
502 

means  of  determining,  40 

minimal,  definition  of,  275 

nitrogen  of  urine  and  feces  a 
measure  of,  22 

in  phlorhizin  glycosuria  and  dia- 
betes mellitus,  452,  453 

in  phosphorus  poisoning  after 
phlorhizin,  492 

in  pneumonia,  table,  520 

during  pregnancy,  387 
and  protoplasmic  mass,  123,  406 
purin,  chapter,  526 
and  radium  emanations,  550 

reduction  by  carbohydrate,  cause 
of,  285,  286 

after  reduction  of  serum  protein, 

83 
reduction  of,  during  hibernation,  116 

relation  of 

oxygen  to,  28,  30,  31 

protein  to  total,  in  starvation,  85 


Metabolism 

respiratory 

and  atmospheric  pressure,  428 
of  carbohydrate,  chapter,  289 
influence  of  protein  food,  chapter, 

223 
"secondary  rise"  in,  on  meat-fat 
diet,  255 
and  seasickness,  150 
of  severe  diabetes,  table,  469 

table,  477 
during  sleep,  100,  no 
in  starvation  of  man,  general  table 

of,  90 
stimulation  of,  and  capacity  to  grow, 

and  strain,  physical,  322 

in  stupor,  438 

and  surface  area,  122 

and  temperature,  117,  135,  147,  234, 

502 
a  theory  of,  301 
and  thyroid,  400,  439 
of  trioses,  262 

in  typhoid  fever,  table,  514 

influence  of  carbohydrates  on, 
table,  516 
and  ultra-violet  rays,  429 
Voit's  views  of,  45 
and  water  drinking,  162 

wear  and  tear,  effect  of  high  body 
temperature  and  increased  heat 
production  on,  501,  502 
wind  upon,  table,  146 

during  work,  315,  317 
work,  effect  of  mechanical,  109,  309, 
310,331 
Metal  workers,  energy  requirements  of, 

34Q 
Methyl-glyoxal 

from  fructose,  1Q4 

glucose  from,  193,  266 

interconversion  of  tautomeric  forms, 
194 

lactic  acid  from,  192,  193,  264,  265 
Metric  and  avoirdupois  weights,  com- 
parison, 574 
Mettenleiter,  322 
Mettler,  see  Sherman,  359 
Meuenzer,  221 
Meyer,  A.  L.,  296 

see  Peabody,  497 
Meyer  and  Du  Bois,  424 
Meyer,  Erich,  see  Langstein,  196 
Meyer,  G.  M.,  see  Levene,  176,  192, 
264,  265,  267 

see  Van  Slyke,  80,  81,  82 
Michaelis,  214 

see  Rona,  161 


INDEX 


621 


Michaelis  and  Kramsztyk,  217 
Miescher 

circulating    protein    during    starva- 
tion, 75 

fat  in  salmon  during  spawning,  249 

origin  of  purins  in  metabolism,  539 
Milk 

absorption   of   ash   constituents  of, 
table,  398 

alcohol  in,  397 

amino-acids   in   different   kinds   of, 
400 

barley  water  in,  400 

caloric  value  of,  385 

composition  of,  399,  412 
and  diet,  391,  395 
and  growth  of  organism,  table,  39S 

diet,  utilization  of,  353,  354 

distribution  of  calories  in,  399 

extractive  substances  in,  399 

fat 

content  of,  during  fasting,  table, 

393 
influence  of  linseed  oil  upon,  394 

as  a  food,  354 

for  growth,  374,  410 

human 

caloric  value  of,  401 
comparison  with  cows',  399 
composition  of,  400 

in  infant  fee'ding,  399,  400 

iron  in,  398 

modified,  401 

nitrogen  and  urinary  nitrogen,  391 

in  obesity,  354 

parental,  value  of,  397 

pasteurized,  and  scurvy,  365 

powder,  absorption  of,  354 

in  pregnane)-,  as  food,  390 

proteins 

biologic  value  of,  table,  374 
comparative  value  of,  for  growth, 

375.376.377 
secretion  of,  in  starving  goats,  106 
theories  regarding  formation  of,  395, 

utilization  of,  table,  399 

value  of.  359 
Miller  and  Jones,  540 
Milner,  see  Benedict,  F.  G.,  38,  272 
Minkowski 

diabetes  after  pancreatectomy,  446 

D  :  N  ratio  in  depancreatized  dog, 
454 

fructose  in  depancreatized  dogs,  485 

hypoxanthin  in  dog,  535 

ingrafted    pancreas    in    pancreatic 
diabetes,  453 

liver  extirpation  in  geese,  541 


Minkowski 
liver    glycogen    in    depancreatized 

dogs,  44S 
summary    of    knowledge    of    gout, 

545 

treatment  of  gout,  551 

urates  in  gout,  549 

uric    acid    excretion    after    hypo- 
xanthin ingestion,  532 

see  von  Mering,  446,  453 
Mitchell,  see  Mendel,  534 
Mituch,  see  Tangl,  380 
Miura,  461 

see  Kumagawa,  71 
Moeiler,  52 
Mohr,  523 
Moleschott,  22 
Mononucleotid,  529 
Moore  and  Parker,  396 
Morgen,  Beger,  and  Fingerling,  393 
Morgen,  Beger,  Fingerling,  and  West- 

hauser,  393 
Moritz 

alimentary  glycosuria 
after  glucose,  449 
after  champagne,  450 

milk  in  treatment  of  obesity,  354 

see  Klein,  222 
Morse,  212 

Mosenthal,  H.  O.,  481 
Mosenthal  and  Richards,  495 
Mosse,  430 
Mother  and  child,  relative  weights  of, 

during  pregnancy,  381 
Motion  and  life,  32 
Moulton,  130 
Mountain  air,  beneficial  properties  of, 

438 
Mountain  climbing,  229 

effect  of  training  in,  427,  431 
persistence  of  acidosis  after,  table, 

434 
Mountain  sickness,  body  temperature 

in,  433 
Muconic  acid 

aceton  bodies  from,  197 
from  benzol,  197 
Mucosa,  intestinal  enzymes  in,  258 
von  Mueller,  Friedrich 

ammonia  excretion  and  acid  forma- 
tion, 214 
cause  of  toxic  destruction  of  protein 

in  pneumonic  phthisis,  513 
composition  of  feces  after  bread  in- 
gestion, 52  _ 
feces  production  after  meat  inges- 
tion, 49 
metabolism  in  exophthalmic  goiter, 
441 


622 


INDEX 


von  Mueller,  Friedrich 

toxic  destruction  of  protein 
in  carcinoma,  512 
in  fevers,  513 
von  Mueller  and  Seemann 

origin  of  sugar  in  diabetes,  172 
von  Mueller,  sec  Bornstein,  434 
see  Helle,  393 
see  Hirsch,  503 
see  Lehmann,  51,  59 
see  Zuntz,  330,  435 
Muenzer,  468 
see  Begun,  220 
see  Loewy,  219 
Munk 
luxus  consumption  of  protein,  336 
metabolism  of  bones  in  starvation, 

.92 
nitrogen  excretion  in  fasting,  90 
see  Lehmann,  51,  59 
Murlin 
alkali  therapy  in  diabetes,  485 
creatin  in  urine  in  pregnancy,  212 
metabolism  of  pregnant  dog,  384 
protein  sparing  by  gelatin,  280 
Murlin  and  Bailey 

ammoniacal      fermentation     and 

bladder  irrigation,  214 
composition  of  urine  in  pregnancy, 

384 
Murlin,  Edelmann,  and  Kramer 

interpretation     of     respiratory 
quotient,  473 
Murlin  and  Hoobler 

energy  metabolism  of  children,  407 
Murlin  and  Kramer 

effect     of     alkali     upon     glucose 
oxidation      in      depancreatized 
dogs,  485 
specific  dynamic  action  of  protein 
in  depancreatized  dog,  474 
Murlin  and  Lusk 

ammonia  elimination  during  car- 
bohydrate metabolism,  296 
specific  dynamic  action  of  fat,  252 
Murlin,  see  Bailey,  404,  406 
see  Carpenter,  3S2 
see  Underhill,  494 
Murschhauser,  135 

see  Benedict,  F.  G.,  312,  329,  331 
see  Schlossmann,  403,  404 
Murschhauser  and  Hiddings,  140 
Muscle,  beef,  caloric  value  of,  39 
Muscle,  see  Work, 
creatin  in,  211 
human,  ash  of,  98 

lactic  acid  in,  under  abnormal  con- 
ditions, 264,  420 
under  normal  conditions,  263 


Muscle 
and    liver,     relation     of    absorbed 
amino-acids,  81 

Mushrooms,   nutritive   value   of   pro- 
teins of,  54 

Mutarotation 
action  of  acid  upon,  261 
phenomenon  of,  260 

Myers  and  Fine,  211,  213 

Myers,  V.  C,  see  Mendel,  528 

Myxedema 
condition  in,  440 
metabolism  in,  418,  443 


Nails 

excretion  of  nitrogen  in,  22 
growth  of,  22 
Naunyn,  541 
fatty  degeneration  in  fever,  521 
treatment  of  diabetes,  479 
Nebelthau 

effect  of  severing  cord,  509 
heat 

loss  in  fever,  510 

retention    and    temperature    in- 
crease, 507 
Nef 
interconversions    of    methylglyoxal, 

104 
products  of  sugar  cleavage,  260 
Nelson,  see  Mathews,  81 

see  Steenbock,  219 
Nencki,  see  Hahn,  536 
Nephritis 

acidosis  in,  496 
metabolism  in,  406 
non-protein  nitrogen  in  blood  in,  495 
salt  in  perspiration  in,  496 
urea  in  blood  in,  495 
uric  acid  in  blood  in,  547 
Neubauer,  O. 
fructose  in  diabetes,  486 
interconversion  of  aceton  bodies  in 

the  body,  465 
process  of  deamination,  177 
wine  in  treatment  of  diabetes,  480 
Neubauer  and  Falta 
homogentisic    acid    in    metabolism, 
196 
Neubauer  and  Fromherz 
oxidative  deamination,  179 
yeast  on  p-oxy-phenyl-pvruvic  acid, 
180 
Neuberg,  Carl,  269 
action  of 

carboxylase,  267 
yeast  zymases  upon  glycol,  191 
i-arabinose  in  pentosuria,  487 


INDEX 


623 


Neuberg,  Carl 
d-glucose  from  d-1-alanin,  193 
lactic  acid  from  methyl-gryoxal,  192 
264,  265 
Neuberg  and  Langstein 

glycogen    and    lactic    acid    from 
alanin,  191 
Neuberg  and  Rewald 

glycocoll  from  glycollic  acid,  190 
origin  of  methyl  groups  in  lactic 
acid  and  alcohol,  193 
Neuberg  and  Ringer 

succinic   acid   from   keto-glutaric 
acid,  202 
Neuberg,  see  Albu,  358 

see  Brasch,  462 
Neutrality,  214 
Nightingale,  366 
Nitrogen 
amino-acid  in  blood  after  plasma- 
pheresis, 83 
assimilable,  how  determined,  335 
in  bacteria,  55 

balance  in  pregnant  dog,  table,  386 
balances  in  typhoid  fever.  514 
in  blood  plasma   in   fasting,   table, 

106 
caloric  value  of  urinary,  38 

in  diabetes,  471 
in  cattle  and  surface  area,  130 
in  cutaneous  excretions  of  man,.  2  2 
and  dextrose  in  phlorhizin  diabetes, 

table,  99 
elimination 

of,  in  fasting  dog,  72 

as  index  of  protein  metabolism, 

167 
influence  of  previous  high  protein 

diet  upon,  table,  275 
after  water  drinking,  162 
equilibrium,  20,  152 
on  bread  alone,  354 
on  calorie-poor  diet,  154 
without  carbon  equilibrium,  154 
definition  of,  153 
with  digested  mixtures,  158,  159 
with  gelatin  plus  deficiencies,  157 
in  hepatic  disease,  403 
and  increasing  quantities  of  meat, 

table.  155 
influence  of 

carbohydrate  upon,  155,  277 
fat  upon,  254 
low   level   of,   in    undernutrition, 

table,  270 
minimal  protein  requirement  for, 

.153-  277,  336 
with  pure  mixed  amino-acids,  159 
and  tryptophan,  159 


Nitrogen 

in  excreta 

in  epidermis  of  dog,  22 
in  feces,  39,  47,  51 
in  hair  of  dog,  22 
in  human  hair,  22 
in  nails,  22 
in  sweat,  22 
in  urine 

in  diabetes,  173 

elimination  as  urea,  20,  165 

in  fasting,  86,  90,  97 

"lag,"  169 

and  magnesium,  98 

after  meat,  per  hour,  164 

and  milk  nitrogen,  391 

partition,  209 

and  phosphorus,  167 

in  pregnancy,  386 

in  sleep,  no 

and  sulphur,  92,  167 

temperature,  influence  of,  137 

work,  influence,  108 
non-protein 
in  blood,  496 

in  arthritis,  547 

in  gout,  547 
retention,  255,  286 
at  high  altitudes,  435 
in  nephritis,  495 
in  pregnane}',  386 
Nolan,  see  Reilly,  107,  156,  172,  455, 

463 
Non-protein  nitrogen,  see  Nitrogen. 
Non-protein  respiratory  quotient,  60 
von  Noorden 

cases  of  severe  diabetes,  484 

effect  of  opium  on  sugar  production 

in  severe  diabetes,  485 
excretion  of  aceton  bodies  during  car- 
bohydrate metabolism,  469 
fructose 

in  intermediary  metabolism,  486 
in  urine  in  severe  diabetes,  446 
glycolysis,  264 

metabolism  in  phlorhizin  glycosuria 
after  thyroidectomy,  460 
von  Noorden  and  Schleip 

tolerance  test  in  gout,  550 
"Normal  controls,"  127 

emaciation  as  a  factor  in  selection 

of,  476 
heat  production  of,  table,  127 
selection  of,  for  comparison  with 
diabetics,  475 
Nucleic  acid 

cleavage  of,  527,  529 
structure  of,  529 
Nucleinase,  529 


624 


INDEX 


Nucleo-protein 

as  food  in  gout,  547 

uric  acid  from,  531 
Nucleosid,  529 
Nucleosidase,  action  of,  530 
Nucleotid,  529,  531 
Nucleotidase,  329 
Nutrition 

definition  of,  69 

development  of  science  of,  18 

reform  in,  Rubner's  ideas  of,  570 
"Nutritive     decline"    on    zein     food, 

chart,  373 
"Nutrose" 

glucose  from,  456 

specific  dynamic  action  of,  406 


OATS,  influence  of,  upon  growth,  370 
Obesity,  256,  257 

acidosis  in,  during  fasting,  table,  94 

and  alcohol,  356 

influence  of  temperature  and  hu- 
midity upon  metabolism  in,  table, 
.147 

milk  in  the  treatment  of,  354 
Occupations,  caloric  value  of  dietaries 

in  various,  346,  347,  349 
Odake,  see  Suzuki,  367 
Oertel,  see  Janeway,  488 
.Offspring,  and  purified  food,  362 
Olive  oil,  influence  of,  on  growth,  369 
Opie,  488 

Opium,  use  of,  in  treatment  of  dia- 
betes, 485 
Oppenheimer 

growth  and  milk  in  food,  410 

d-lactic  acid  from  d-fructose,  264 

lactic  acid  from  trioses,  265 
Oppenheimer  and  Reiss 

body  changes  in  scarlet  fever,  522 
Oppenheimer,  see  Griesbach,  176 
Optimum  protein  condition  of  cells,  287 
Organism 

growth  of,  and  composition  of  milk, 
table,  398 

synthetic  production  of  certain  sub- 
stances by,  371 
Organs 

loss  of  weight  in  different,  during 
starvation,  table,  105 

temperature  of  inner,  132 
Ornithin 

from  d-arginin,  204 

glucose  from,  204 

putresin  from,  204 
Orr,  see  Carlson,  453 
Osborne 

analysis  of  muscle,  207 


Osborne 

concerning  crystalline  vegetable  pro- 
teins, 77 
Osborne  and  Jones 

analysis  of  proteins,  78 
composition  of  ox  muscle,  77 
Osborne  and  Mendel 

bacterial  nitrogen  in  feces,  55 
comparative  composition  of  pro- 
teins, 77 
growth 

butter  fat  on,  369 
casein  on,  376 

diet  upon  stunted  animal,  375 
gliadin  on,  375 
lactalbumin  on,  376 
lysin  on,  375 
maize  on,  373 
protein  free  milk  on,  368 
with  purified  food  materials,  362 
zein  on,  372 
Osmosis,  82 

Osterberg,  see  Benedict,  S.  R.,  212 
Ostertag  and  Zuntz,  385,  412 
Oswald,  492 
Ott,  525 
Ovalbumin,    glucose    derivable    from, 

457 
Ovarian    insufficiency    and    chlorosis, 

438 
Oxidation 
/?-carbon  of  fats,  182,  183 
Crawford's  experiments  on,  33 
reduced,  31,  491 
of  unsaturated  fatty  acids,  183 
Oxidations  in  body,  where  performed, 

3i,4i8 
Oxy-acids    and   specific    dynamic   ac- 
tion, 245 
Oxy-aldehydes,  action  of  yeast  upon, 

191 
^-oxybutyric  acid 

from  aceto-acetic  acid,  466 

from  butyric  acid,  465 

and  coma,  465 

conditions  for  oxidation  of,  271 

in  diabetic  tissues,  467 

effect  of  sodium  bicarbonate  on 

elimination  of,  484 
excretion  of 

in  obesity  during  fasting,  94 
in  starvation,  table,  93 
from  fat,  183,  250 
fate  of  ingested,  in  diabetes,  465, 

466 
from  histidin,  205 
from  leucin,  195 
from  lysin,  203 
from  neutral  fat,  465 


INDEX 


625 


/?-oxybutyric  acid 

in  normal  blood,  250 

from  phenylalanin,  195,  197 

source  of,  in  diabetes,  464,  465, 

466 
from  tryptophan,  205 
from  tyrosin,  195,  197 
Oxygen 
absorption 

in  apnea,  Pfliiger's  experiment,  32 
of,  in  curarized  dog,   at   various 

temperatures,  curve,  115 
of,  in  fasting,  86 

of,  after  glycocoll  in  normal  con- 
ditions, 245 
alveolar    tension    of,    at    different 

levels,  table,  432 
caloric  value  of,  61 
cause  of  consumption  of,  28,  30,  31 
discovery  of  true  importance,  18 
inhalation  of,  and  fatigue,  419 
lack  of 

and  lactic  acid  in  urine,  427 
and  respiration,  428 
relation  of  metabolism  to,  28,  30,  31 
respiration  of  pure,  and  metabolism, 

419 
tension,   and   oxygen-absorbing   ca- 
pacity of  blood,  432 
Oxyhemoglobin 
dissociation  of,  at  high  body  tem- 
peratures, 433 
reduction  of,  death  from,  434,  435 
a-Oxyisovalerianic  acid,  195 
p-Oxy-phenyl-lactic  acid,  181,  182 
in  alcaptonuria,  178 
from   p-oxy-phenyl-pyruvic   acid, 
180 
p-Oxy-phenyl-pyruvic  acid,  182 
action  of  yeast  upon,  180 
homogentisic  acid  from,  178 
p-oxy-phenyl-lactic  acid  from,  180 


PAECHTNER,  see  Voeltz,  397 
Painters,  energy  requirements  of,  349 
Palmer,  Means,  and  Gamble,  211 
Palmer,   see    Henderson,   L.    J.,    217, 

361,  496 
Palmitic  acid  from  glucose,   reaction, 

268 
Pancreas 

effect  of  incomplete  removal  of,  453 

extirpation  of,  and  diabetes,  446 

pathology  of,  in  diabetes,  488 

pentose  from,  4S7 
Pancreatectomy 

D  :  N  after,  in  dogs,  454 

glucose  oxidizing  power  lost  in,  448 

40 


Pancreatectomy 

and  liver  glycogen,  448 
partial,  453 
Parabiosis,  experiment  on,  453 
Parathyroidectomy 
effect  of,  444 
calcium  on,  444 
Parhon,  442,  461 
Paris,  siege  of,  and  scurvy,  365 
Parker  and  Lusk,  186 
Parker,  see  Moore,  396 
Parnas  and  Baer,  190 
Parnas  and  Wagner,  264 
Partridge,  see  Jones,  533 
Parturition 
and  creatin  in  urine,  212 
metabolism  before  and  after,  table, 
382 
Patein  and  Daval,  399 
Pawlow,  see  Hahn,  536 
Peabody,  496 

Peabody,  Meyer,  and  Du  Bois,  497 
Peasant,  Finnish,  dietary  of,  348 

Italian,  dietary  of,  342 
Peiigot,  446 
Pellagra 
antidotes  for,  366 
and  corn,  366 
possibly  infectious,  366 
mortality  in,  366 
and  potatoes,  366 
prevalence  of,  366 
Pembrey 
bloodletting,  422 
studies  in  hiberation,  306 
.  sugar  from  fat,  472 
Pentoses,  488 
Pentosuria,  487 
Pepper  and  Austin,  167 
Pepsinogen,  105 
Peptids,  definition  of,  75 
Peptone,  type,  structure  of,  76 
Perspiration 
in  fever,  511 
insensible 

earhy  conception  of,  17 
experiment  of  Sanctorius,  17 
loss  of  water  in,  131,  132 
von  Pesthy,  see  Hari,  123 
Pettenkofer 

respiration  apparatus,  23 
Pettenkofer  and  Voit 

carbon   retention   after   meat   in- 
gestion, 223,  228 
combustion  of  fat  during  work,  109 
early  work  on  isodynamic  law,  36 
metabolism 

in  acute  leukemia,  424 
in  diabetes,  473 


626 


INDEX 


Pettenkofer  and  Voit 

metabolism 
in  fasting,  26 
during  work.  310 
relation   of   carbon   and   urea  in 
urine,  37 
Pfeil,  542 
Pflueger 

D  :  N  ratios  in  depancreatized  dogs, 

454 
effect   of   high   environmental   tem- 
perature upon  metabolism,  500 
fat  in   liver   after  ingestion  of  fat, 

glycogen  in  body  during  starvation, 

107 
lung  ventilation  and  carbon  dioxid 

elimination,  32 
polemic  on  Voit's  work,  228 
protein  as  sole  diet,  152 
reduced  metabolism  in  frogs,  419 
sugar  from  fat  in  diabetes,  457 
Pflueger  and  Junkersdorf 

glucose  from  protein,  175 
Phenaceturic  acid,  how  formed,  182 
Phenol,  excretion  of,  207 
Phenyl-acetic  acid,  1S3 
Phenyl-alanin 
action  of  bacteria  upon,  179 
fate  of,  195 
glucose  from,  197 
homogentisic   acid   from,    178,    195, 

196 
occurrence  of,  195 
/3-oxybutyric  acid  from,  195,  197 
phenyl-ethyl-amin  from,  179 
tyrosin  from,  195,  196 
Phenyl-ethyl-amin,  179 
Phenyl-glycocoll,  177 
Phenyl-glyoxylic  acid,  177 
Phenyl-} -keto  butyric  acid,  183 
Phenyl-o-keto  propionic  acid,  183 
Phenyl- ^-keto-propionic  acid,  183 
Phenyl-3-oxy-propionic  acid,  183 
Phenylpropionic  acid,  183 
Phenyl-pyruvic  acid,  183 
Phloretin,  324 
Phlorhizin 
action  of 

on  colloidal  blood  sugar,  452 
in  phosphorus  poisoning,  263 
and  body  glycogen,  107 
glucose  in  bile  after,  451 
glycosuria,  influence  of  fructose  in, 

table,  296 
influence  of 

upon  lactose  in  milk,  395 
in    protein    metabolism    in    phos- 
phorus poisoning,  492 


Phosphates,  acid,  effect  upon  urinary 

ammonia,  222 
Phosphorus 
and     nitrogen     elimination,     table, 

167 
and  nitrogen  ratio  in  urine  in  star- 
vation, 92 
organic,  influence  on  growth,  371 
Phosphorus  poisoning 

action  of  phlorhizin  in,  263,  492 
amino-acids  in  liver  after,  492 
autolysis  in,  492 
and  creatin  in  urine,  212 
and  creatinin  elimination,  210 
fasting,  heat  production  in,  491 
fat  changes  in,  491 
lactic  acid  in,  263,  493 
Physical  regulation,  235 

of  body  temperature  in  fever,  510, 

511 
Pigeon,  metabolism  of,  without  feath- 
ers,  138 
Pigs,  suckling,  growth  of,  in  relation 

to  milk  ingested,  table,  410,  411 
Pike's  Peak 

expedition  to,  430 
heat  production  in  climbing,  431 
Pincussohn,  see  Adberhalden,  81 
Piqfire,  445,  447 

Pituitary  in  hibernating  animals,  439 
Plasmapharesis 

definition  of,  83 

effect  of.  upon  composition  of  blood, 
table,  83 
Plethora 

carbohydrate,  302 

carbohydrate  and  fat,  303 

and  amino-acid  stimulation,  303 

fat,  301 
Plimmer,  76 
Pneumonia 

protein  metabolism  in,  table,  520 

salt  retention  in,  522 
Poda,  see  Helle,  393 
Poisoning,  carbon  monoxid,  hemoglo- 
bin in,  434 
Pollak,  545 
Polyneuritis 

in  pigeons,  362 

and  yeast  vitamins,  367 
Polynucleotid,  529 
Poor,  the,  living  expenses  of,  in  N.  Y. 

City,  table,  557 
Poorhouse    in     Finland,    dietary    of, 

35i 
Porges,  219 

Porges  and  Salomon,  472 
Posture,  effect  of,  upon  metabolism, 

table,  331 


INDEX 


627 


Potassium 

excretion  of,  in  fasting,  92,  93 

retention  of,  at  high  altitudes,  435 
Potato 

protein,  utilization  of,  341 

value  in  dietary,  340 

and  pellagra,  366 
Poulton,  221,  468 

see  Graham,  501 
Power 

adaptive,  of  organism,  96 

physical,  maintenance  of,  and  pro- 
tein ingestion,  318 
Pratt,  see  Benedict,  F.  G.,  231 
Prausnitz 

digestibility  of  animal  and  vegetable 
foods,  52,  54 

glycogen  in  body  after  fast  and 
phlorhizin  injection,  107 

influence  of  glycogen  content  of 
body  upon  metabolism  in  star- 
vation, 72 

see  Helle,  393 
Pregnancy 

composition  of  urine  during,  384 

in  dogs,  metabolism  during,  table, 

38S 
importance  of  milk  in  diet  during, 

390 
nitrogen 

balance  in  dog  during,  table,  386 

loss  during,  386 

retention  during,  table,  386 
oxvgen  consumption  during,  table, 

protein  metabolism  during,  387 

relative  weights  of  mother  and  child 
during,  381 

von  Winckel's  diet  for,  384 
"Premortal  rise,"  91 

law  of,  101 
Pressure,    barometric,     influence     of, 

upon  efficiency  for  mechanical  work, 

332,  426 
Prevost  and  Dumas,  495 
Priestly,  see  Haldane,  217 
Prolin 

fate  of,  205 

glucose  from,  205 

occurrence,  205 
Prommsdorfl,  see  Frank,  223 
Propionic  acid,  467 
Protein 

absorption  of,  157 

allowance  of.  and  physical  develop- 
ment, 341,  342 

assimilable,  how  determined,  335 

in  Atwater's  laborer's  ration,  335, 
336 


Protein 

banana,  utilization  of,  355 

benefits  of  ample  quantity  in  dietary, 

337 
body 

biscuit  meal  proteins,  as  sparers 
of,  282 

protection  by  ingested  protein,  287 
bread,  utilization  of,  341 
caloric  value  of,  in  nutrition,  Rub- 

ner's  experiment,  40 
carbohydrate  from,  226 

proof  of,  227,  229 
circulating 

definition  of,  74 

experiments  on,  74,  75 
cost  and  energy,  table  of,  575 
"deposit,"  84 

and  "circulating,"  85 

elimination  of,  84 

in  fasting,  85 
deposit  of,  and  metabolism,  245 
in  dietary 

during   lactation,   importance   of, 

394 
of  German  soldier,  343 
regulation  of,  344 

digestion,  rapidity  of,  242,  243 

D   :  N  after  ingestion   of  various, 
table,  456 

"dynamic  quota,"  definition  of,  277 

early  production  of  glucose  from,  174 

effect  of,   upon  heat  production  of 
curarized  dogs,  246 

egg,  during  incubation,  380 
.  energy 

from,  in  starvation,  86 
from,  in  work,  277 
furnished  in  rest,  277 

excessive 

and  carbon  retention,  223,  226 
influence  upon  metabolism,  223 
metabolism  after  (R.  Q.  indirect, 
direct  nitrogen  chart),  224 

experimental,     calculation    of    res- 
piratory quotient,  60 

fat  from,  228,  229,  230 
by  Calliphora,  230 

and  fat,  iso  dynamic  relations,  257 

fatty  degeneration  of,  489 

food 

and  blood  protein,  160 
influence  of,  chapter,  152 

glucose  from,  calculation,  table,  207 

glycogen  from,  171 

"growth  quota,"  definition  of,  276 

heat  value  of,  in  metabolism,  40 

high,   and   nitrogen  balance  in   ty- 
phoid fever,  table,  515 


628 


INDEX 


Protein 

hunger,  definition  of,  69 
"improvement     quota,"     definition 

of,  276 
ingested,  protection  of  body  protein, 

287 
ingestion 

influence  of  external  temperature 
on  metabolism  after,  table,  234 
and  maintenance  of  physical  pow- 
er,   318 
Italian  laborers,  dietary  of,  335 
from  lean  meat  by  pressure,  75 
loss  of,  in  "repeated  fast,"  104 
low  dietary  of 

Abderhalden's  views  of,  343 
advisability  of,  339,  343 
Chittenden's    work,    337,    338, 

339,346,347. 

and  creatinin  elimination,  272 

Rubner's  views  of,  342 

Voit's  views  of,  343 
lumbermen's  dietary  of,  336 
luxus  consumption  of,  337 
metabolism 

and  amino-acids,  78,  79 
in  anaphylaxis,  161 
in  artificial  anemia,  421 
character    of,     during     muscular 

work,  table,  316,  317 
before  and  after  childbirth,  table, 

388 
conditions  of,  288 
in  diabetes,  influence  of  thyroid 

on,  460 
and  diminished  atmospheric  pres- 
sure, 427 
in  dogs  during  work,  table,  108 
endogenous,  209 

ammonium  acetate  as  sparer  of, 
283 

ammonium  chlorid  as  sparer  of, 
284    _ 

ammonium  citrate  as  sparer  of, 
283 

carbohydrate  as  sparer  of,  275 

gelatin  as  sparer  of,  283 

urea  as  sparer  of,  284 
exogenous,  209 
in   fever,   action   of   protein   and 

carbohydrate  ingesta  upon,  501 
glycocoll  stage  of,  188 
indexed  by  nitrogen  elimination, 

167 
influence  of 

carbohydrate  on,  table,  269,  270 

diabetes  upon,  table,  463 

fat  upon,  248 

glycogen  in  fasting,  72,  73 


Protein 

metabolism 

intermediary,  chapter,  171 
early  views  of,  171 

and  kynurenic  acid,  206 

loss  of  body  weight  in  exclusive, 
102 

lower  limit  of,  compatible  with 
life,  282 

in  man,  effect  of  high  environ- 
mental temperature  upon,  table, 
502 

measured  by  urinary  and  fecal 
nitrogen,  22 

and  total  metabolism,  85 

minimal,  definition  of,  275 

in  phlorhizin  glycosuria  and  dia- 
betes mellitus,  452,  453 

in  phosphorus  poisoning  after 
phlorhizin,  492 

in  pneumonia,  table,  520 

during  pregnancy,  387 

reduction  by  carbohydrate,  cause 
of,  285,  286 

after  reduction  of  serum  protein, 

"secondary    rise"    in,    on    meat- 
fat  diet,  table,  255 
in  severe  diabetes,  463,  464 
of  Succi  during  work,  109 
and  thyroid  ingestion,  440 
in  typhoid  fever,  chart,  514 

influence  of  carbohydrates  on, 
table,  516 
during  work,  315,  317 
milk  fat  from,  390 
of  mushroom,  54 
organized 

definition  of,  74 
experiments  on,  74,  75 
potato,  utilization  of,  341 
quantitative     relation     of     glucose 

formation,  174 
regeneration,  161 
"repair  quota" 

definition  of,  276 
of,  how  best  administered,  282 
replacement    of,    by    gelatin,     156, 

iS7 
respiratory  quotient  of,  29 
retention 

upon  what  dependent,  287 

of,  in  growth,  403 

influence  of  carbohydrate  on, 
table,  269,  270 

during  menstruation,  381 

by  prematurely  born  infants,  390 

during  work,  317 
in  Rubner's  laborer's  ration,  335 


INDEX 


629 


Protein 

similarity  of  composition  from  dif- 
ferent sources,  Osborne's  views,  77 
as  sole  source  of  energy  in  the  body, 

316 
sparing  by  ammonium  salts,  283 
by  carbohydrates,  270,  273,  274 
by  fat,  ico-103 
by  gelatin,  282,  373 
specific  dynamic  action  of,  232,  233, 
234,  236 
cause  of 

Lusk's  views,  244,  245 
views  of  Voit  and  Rubner, 

239 
and  glucose  from,  243 
intensity  of,  243 
in  pancreatic  glycosuria,  474 
in  phlorhizin  glycosuria,  474 
theory  of,  240 
structure  of,  75,  76 
sugar  from,  in  diabetes,  172 
sulphur  from,  in  urine,  92 
superimposed,  168,  169 
synthesis  of,  by  lower  organism,  285 
synthetic   formation   within   organ- 
ism, 284 
toxic  destruction  of 

in  infectious  fevers,  512,  513,  515 
in  tuberculosis,  513 
vegetable  retention  of,  374 
in  Voit's  laborer's  ration,  335,  336 
"wear  and  tear" 

effect  of  high  body  temperature 
and   increased   heat   produc- 
tion on,  501,  502 
quota  of,  276 

quota,  irreducible  minimum  of, 
282 
Proteins 
biologic,  values  of  various,  table,  371 
biscuit  meal,  as  body  protein  sparer, 

282 
"deficient,"  consideration  of,  285 
milk 

biologic  value  of,  table,  374 
comparative  value  of,  for  growth, 
375,  370,  377 
rapidity  of  destruction  of  various, 

168 
specific  dynamic  action  of  various, 

238 
value  of  various,  in  growth,  378 
various 

comparative  value  of,  for  growth, 

chart,  376 
quantities  of  glucose  from,  456, 

457 
sparing  power  of,  table,  371 


Proteins 

vegetable,  78 

biologic  value  of,  table,  374 

wheat,    comparative    value   of,    for 
growth,  375 
Protoplasmic    mass    and    metabolism, 

406 
d-Pseudo-fructose,  from  glucose,  260 
Puberty,    basal    metabolism    of    boys 

during,  129 
Pulay,  see  Schwarz,  269 
Pulse-rate  in  fasting,  90 
Purgatives,  see  Cathartics. 
Purin-free   diet,  chemical  comparison 

of  urines,  574 
Purins,  526 

and  aseptic  fever,  523 

autolytic  production  of,  531 

in  blood,  549 

endogenous,  539 

influence  of  exercise  upon  excretion 
of,  542 

exogenous,  539 

fate  of,  ingested,  538 

in  fever,  524 

metabolism,  chapter,  526 

in  pig  urine,  534 

and  pyrimidin  bases,  528 

retention  of,  in  alcoholics,  545 

synthetic  origin  of,  539 

in  tissues,  table,  541 

"tolerance"    in    gout,     table,    550, 

551 
in  urine  from  food  accessories,  532 
in  urines  of  various  animals,  table, 

537 
Putresin,  from  ornithin,  204 
Pyrimidin  bases 
fate  of,  528 
formulae  of,  527 
and  purins,  528 
Pyrimidin  nucleosids,  action  of  nucleo- 
sidase on,  530 
Pyrrolidin  carboxylic  acid 

chlorophyll  from,  203 
from  glutamic  acid,  202 
hemoglobin  from,  203 
Pyruvic  acid 

action  of  leukocytes  on,  192 

alanin  from,  194 

from  aspartic  acid,  201 

glucose  from,  192 

from  keto-succinic  acid,  201 

lactic  acid  from,  180,  181 


QUAGLIABIELLO,  504 

Quincke,  132 

Quotient,  see  Respiratory  quotient. 


630 


INDEX 


Race  characteristics  and  climate,  148 

Ranke,  344 

Rat,  bacterial  fecal  nitrogen  of,  55 

Ration 

Atvvater's  protein,  for  laborer,  335, 
336 

Rubner's  protein,  for  laborer,  335, 
336 

Voit's,  for  laborer,  335,  336 
Rauber  and  Voit,  150 
Raucken  and  Tigerstedt,  132 
Raulston  and  Woodyatt,  484 
Ravold  and  Warren,  196 
Ray,  McDermott,  and  Lusk,  492 
Reach,  547 

see  Frentzel,  326 
Reale,  39 
Reform  in  nutrition,  Rubner's  ideas  of, 

57o 
Regnault  and  Reiset 

early  respiration  experiments,  21, 

23 
early  writings  of,  19 
energy  metabolism  during  hiber- 
nation of  marmot,  116 
value  of  respiratory  quotients,  57 
Reichel,  see  Brezina,  328,  329,  335 
Reilly,  Nolan,  and  Lusk 
D  :  N  ratio 

after    meat    in    phlorhizin 

glycosuria,  172 
in  phlorhizin  glycosuria  in 
dog,  4ss 
in  rabbit,  455 
glucose  from  gelatin  in  diabetes, 

glycogen  in  liver  in  phlorhizin 

glycosuria,  107 
influence  of  diabetes  on  protein 
metabolism,  463 
Reimbach,  see  Hirsch,  449 
Reiset,  see  Regnault,  19,  21,  23,  57,  116 
Reiss,  see  Oppenheimer,  522 
"Repair  quota" 
of  protein 

how  best  administered,  282 
definition  of,  276 
Reproduction,  see  Growth. 
Residues,  undigested,  in  feces,  52,  54 
Respiration 
apparatus 

of  Pettenkofer  and  Voit,  23 
portable,  of  Zuntz,  87 
bell-jar    experiments    of    Regnault 
and  Reiset  on  CO2  excretions,  23 
calorimeter 

Atwater-Rosa,  chapter,  56 
improved  Atwater-Rosa,  descrip- 
tion of,  63 


Respiration 

Cheyne-Stokes  types  of,  at  high  alti- 
tudes, 430 
effect  of 

sun's  rays  upon,  150 
ultra-violet  rays  upon,  150,  429 
and  hydrogen-ion  concentration  of 

blood,  218 
with  oxygen  lack,  427,  428 
regulation  of,  32 

voluntary  volume  and  COi,  Lossen's 
experiment,  31 
Respiratory   center  and  alveolar  CO2 

tension,  217 
Respiratory  gases,  heat  value  of,  62 
Respiratory  quotient 

after  alcohol  ingestion,  357 
at  birth,  404 
for  carbohydrate,  29,  58 
of  carbohydrate  conversion  to  fat, 
306 
explanation  of,  306 
from     carbohydrate,     theoretical 

derivation  of,  58 
definition  of,  57 
in  diabetes,  470,  472,  480 
for  fat,  29,  58 
human,  59 

in  severe  diabetes,  472 
from  fat,  theoretical  derivation  of, 

S8  . 
after  injection  of  epinephrin,  460 

and  intensity  of  metabolism,  308 

interpretation  of,  472,  473 

from  lard,  59 

non-protein 

calculation  of,  60 

in  severe  diabetes,  471 

for  protein,  29,  60 

range  of,  58,  61 

during  severe  work,  321 

Rest,  see  Basal  metabolism. 

carbon     dioxid     excretion     during, 

table,  no 

energy    furnished   from   protein  in, 

277 

Retzlaff,  see  Umber,  538 

Rewald,  see  Neuberg,  190,  193 

Rhamnose 

fat  sparing  by,  488 

fate  of,  488 

Rheinboldt,  440 

d-Ribose 

from  guanosin,  529 

in  urine,  487 

Rice 

and  beri-beri,  362 

bran  and  beri-beri,  367 

and  polyneuritis  in  pigeons,  362 


INDEX 


631 


Richards,  see  Jones,  530 

see  Mosenthal,  495 
Riche  and  Soderstrom,  44,  63 
Riche,  see  Williams,  224 
Richet,  see  Hanriot,  86 
Rieder,  51 

Riesser,  see  Hensel,  197 
Rigor  mortis,  lactic  acid  during,  263 
Ringer 
adrenalin    injections    in    phlorhizin 

glycosuria,  458 
fate  of  glutaric  acid,  203 
from  fatty  acids,  184 
glucose 

from  alanin,  182 
in  phlorhizin  glycosuria,  452 
from  propionic  acid,  467 
from  pyruvic  acid,  192 
hemoglobin  with  carbon  monoxid,  434 
hippuric  acid,  186 
Ringer,  Frankel,  and  Jonas 
fate  of  lysin,  203 
glucose  from 

malic  acid,  201 
succinic  acid,  202 
Ringer  and  Lusk 

fate  of  tyrosin,  197 
glucose  from 

i-alanin,  191 
aspartic  acid,  200 
glyceric  acid,  193,  198 
glycocoll,  188 
Ringer,  see  Austin,  451  .- 

see  Sweet,  451 
Robertson,  106 
Rockwood 
effect  of  drugs  on  uric  acid  elimina- 
tion, 549 
endogenous    uric    acid   and    caloric 

value  of  diet,  540 
excretion  of  purins,  542 
see  Mendel,  161 
Roehmann,  362 
Roehrig  and  Zuntz,  115,  120 
Roily 

cause  of  fever  in  infectious  fever,  503 

"heat  puncture,"  503 

hemoglobin  in  experimental  anemia, 

423 
metabolism   in   chlorosis   and   mild 

anemias,  424 
respiratory  metabolism  in  typhoid, 

value  of  various  forms  of  starch  in 

diabetes,  483 
see  Hirsch,  503 
Rona  and   Michaelis,  influence  of  in- 
jection of  horses'  serum  into  dogs, 
161 


Rona  and  Wilenko 

acidosis  and  glucose  utilization  by 

beating  heart,  261 
hydrogen-ion      concentration     of 
blood  in  diabetes,  468 
Rona,  see  Abderhalden,  158,  159 
Rontgen   rays  and  uric   acid  produc- 
tion, 549 
R.  Q.,  see  Respiratory  quotient. 
Rosa,  44 

see  Atwater,  56 
Rose,  see  Mendel,  212 
Rosenfeld 

fat    in   body   fluids   during  fasting, 

106 
fatty      degeneration      of      protein, 

.  489 

liver  fat  after  fat  ingestion,  249   ■ 
Rosenfeld  and  Asher 

colloid  glucose  in  blood,  452 
Rosenheim,  336 
Rosenthal,  F.,  522 
Rossi,  see  Albertoni,  342 
Rost,  413 

Roth,  see  Benedict,  F.  G.,  127 
Roth,  see  Fuchs,  460 
Rowntree,  see  Abel,  81 

see  Levy,  219 
Rubner 
amount  of  protein 

for  average  laborer,  335 
for  hard  labor,  336 
baths  upon  metabolism,  500 
caloric  value  of 
feces,  53,  54 
protein  in  nutrition,  40 
urine,  38 
calorimetric  observations,  37 
carbon  dioxid  elimination  after  in- 
gestion   of    large    quantities    of 
meat,  223 
chemical  regulation.  134,  135 

during  mechanical  work,  312 
clothes  on  metabolism,  140 
cold  on  metabolism  in  man,  143 
compensation  theory,  236 
C  :  N  in  meat,  228 
conditions  of  "wear  and  tear"  and 
"growth  quota"  of  protein  met- 
abolism, 413 
correction   in  diet   for   specific   dy- 
namic action,  239 
critical  temperature,  135 
"Darmarbeit,"  231 
death  from  thirst,  70 
direct  and  indirect  calorimetry  with 

dog,  43 
dynamic  action,  43 
eggs  as  sole  diet,  353 


632 


INDEX 


Rubner 

energy 

metabolized     from     maturity    to 

death  in  various  animals,  415 
requirement   of   men    of    various 
weights  while  doing  light  work, 
334. 
retention  for  growth,  415 

excretion  of  nitrogen,  sulphur,  and 
phosphorus  after  meat  ingestion, 
167 

feces  marking  by  milk,  48 

food  reform,  570 

growth  quota  on  protein  metab- 
olism, 276 

hair  and  physical  regulation,  136, 
i37 

hospital  dietaries,  351 

improvement  quota  of  protein,  277 

influence  of 

bath  at  33°  C.  on  metabolism,  237 
cold  baths  on  metabolism  in  man, 

. I43 
diet  and   mechanical   work  upon 

the  metabolism  of  man,  311 
external    temperature   on    metab- 
olism   after    protein    ingestion, 

233 
fat   ingestion   on   nitrogen   reten- 
tion, 254 
humidity  on  metabolism,  139,  148 
the  state  of  nutrition  on  appetite 
and   capacity   for   digestion   of 
dogs,  344 
temperature 

and   humidity   on    the   metab- 
olism of  a  fat  man,  146 
on  manner  of  heat  loss,  140 
on  metabolism  of  fat  and  lean 
dog,  138 
warm    baths    on    metabolism    in 
man,  144 
the  iso  dynamic  law,  36 
law  of 

constant  energy  expenditure,  413 
surface  area  at  low  temperature, 
121 
Liebig's  extract,  352 
manner  of  heat  loss  at  different  en- 
vironmental temperatures,  140 
meat  as  sole  diet,  156 
metabolism 

of  the  obese  and  thin,  256 
during  pregnancy,  381 
and  surface  area,  41,  119 
milk  as  sole  diet,  353 
municipal  food  statistics,  350 
nitrogenous  and  caloric  equilibrium 
with  bread,  354 


Rubner 

outlets  for  heat  loss,  131 

percentage 

composition  of  cows'  milk,  399 
distribution  of   calories   in    milk, 

399. 

phlorhizin  metabolism,  474 
physiologic  utilization  of  milk,  398 
protein 

deposit  and  specific  dynamic  ac- 
tion, 245 
retention  after  milk  ingestion,  279 
radiant  energy  of  sun,  149 
relation  of  area  of  body  surface  to 
cell  surface  and  heat  production, 
121 
relationship  of  weight  to  surface  in 

various  animals,  119 
repair  quota  of  protein,  276 
"secondary"  rise,  233 
"secondary    dynamic    rise"    in    fat 

metabolism,  256 
specific  dynamic  action 
of  fat,  252 

of  different  food-stuffs,  238 
of  protein,  232,  238,  239 
"standard  values,"  43 
starch   in   feces   after  ingestion   of 

potatoes,  52 
theory  of  metabolism,  301 
variety  in  dietary,  342 
"wear  and  tear"  quota  of  protein 

metabolism,  102,  275 
wind  and  heat  loss,  145 
yeast,  293 
Rubner  and  Heubner 

energy  retention  in  growth,  412 
extractive  nitrogen  in  human  and 

cows'  milk,  399 
metabolism  of  differently  condi- 
tioned children,  401,  402,  403 
percentage  composition  of  human 

milk,  399 
respiration    experiment    on    child 
nourished  with  modified  cows' 
milk,  403 
Rubner  and  Langstein 

metabolism  of  prematurely  born 
infants,  390 
Rudinger,  see  Eppinger,  458,  460 
Running,  energy  requirements  during, 

329 
Rye,  influence  of,  upon  growth,  370 
Ryffel,  421 


Saccharin,  561 
Salaskin,  22 
Salkowski,  535 


INDEX 


633 


Salmon 

fat  in,  during  fasting,  249 
Meischer's  experiments,  75 
Salomon,  see  Embden,  194,  195,  197, 

454 

see  Porges,  472 

see  Wallace,  51 
Salt 

daily  requirement  of,  359 

metabolism    of    growing    children, 
table,  417 

in  perspiration  in  nephritis,  496 

retention  in  fever,  522 
Salts 

milk,  influence  of 

upon  growth,  374 
on  composition  of  milk,  395 
Samuely,  see  Abderhalden,  160 
Sanctorius,  17 
Sandelowsky,  522 
Sanford,  410 

Sansum  and  Woodyatt,  190 
Sass,  263,  493 
Sassa 

glycocoll  from  glycollic  acid,  190 

3-oxybutyric  acid,  J50 

in  tissues  in  diabetes,  467 
Sawadowsky,  510 
Scaffidi,  213 
Schaefer,  395 

Schaeffer,  see  Armand-Delille,  285 
Schapals,  145 
Schapiro,  41 2 
Schittenhelm 

on  enzymotic  activity,  532 

purin  oxidations  in  tissues  of  cattle, 

534 
Schittenhelm  and  Bendix 

uric  acid  in  pigs'  urine,  534 
Schittenhelm,  see  Abderhalden,  536    • 

see  Kuenzel,  534 
Schlaepfer,  see  Grafe,  284 
Schliep,  see  Von  Noorden,  550 
Schlossmann,  caloric  value  of  human 

milk,  401 
Schlossmann  and  Murschhauser 
metabolism  of  infants,  404 
protein  for  growth,  403 
Schmid,  see  Krueger,  532 

see  Linser,  500 
Schmidt,  see  Bidder,  20,  36,  171,  223 

see  Embden,  194,  195,  197 
Schmitz,  see  Embden,  194,  198,  264, 

265 
Schneider,  see  Douglass,  427,  430 
Schoendorfif,  100,  259 
School     children,    undernutrition    of, 

cause  of,  559 
Schrader,  381 


Schreuer,  226 

von  Schrotter  and  Zuntz,  428 

Schryber,  493 

Schuermann,  36 

Schultz,  H.,  114 

Schultzen,  91 

Schulz 

blood  fat  in  starvation,  249 

fat 

and  protein  retention,  104 
in  starvation,  103 
Schumburg,  324,  325 

see  Zuntz,  62,  316,  331,  430 
Schumm,  196 

see  Hartogh,  457 
Schur,  see  Burian,  539,  541 
Schwarz  and  Pulay,  269 
Schweisheimer,  357 
Schwenkenbecker  and  Inagaki,  511 
Scurvy 

experimental  production  of,  365 

fruit  juices  in,  365 

and  pasteurized  milk,  365 

relief  from,  365 
Seamstresses,  energy  requirement  for, 

349 
Seasickness,  effect  upon  metabolism, 

150  ■ 

"Secondary  rise"   in  protein  metab- 
olism, 255 
Secretion 

internal,  439 

milk,  106,  391 
Seegen,  91 
Seelig,  462 

Seemann,  see  von  Mueller,  172 
Seidell,  see  Williams,  378 
von  Seiller,  see  Breuer,  438 
"Self  regulation,"  293 
Selling,  see  McLean,  166 
Senator,  506 

see  Lehmann,  51,  59 
Serin,  from  cystein,  200 
1-Serin,  198 

d-glyceric  aldehyd  from,  198 

glucose  from,  198 

glyceric  acid  from,  198 
Serum     albumin,     glucose     derivable 

from,  457 
Servants,   household,   energy  require- 
ments of,  349 
Severin,  see  Forschbach,  439,  442,  459 
Sex, 129 

Seymour,  see  Folin,  496 
Shaffer 

creatin  in  urine  after  parturition,  212 

creatinin  coefficient,  210 

muscular   work   upon   character   of 
protein  metabolism,  316 


634 


INDEX 


Shaffer  and  Coleman 

carbohydrate  diet  in  typhoid,  516 
Sherman  and  Gettler 

acid  and  base  forming  potency  of 
ash  of  foods,  361 

ash  content  of  edible  foods,  360 
Sherman  and  Hawk 

elimination  of  sulphur  and  nitro- 
gen on  mixed  diet,  170 
Sherman,  Mettler,  and  Sinclair 

salt  content  of  ordinary  Amer- 
ican diet,  359 
Shibata,  491 

Shimamura,  see  Suzuki,  367 
Shivering  and  chemical  regulation,  143 
Shohl,  see  Cannon,  449 
Silbergleit,  550 
Simpson,  S.,  439 

see  Goldbraith,  113 
Simpson,  S.,  and  Herring,  116 
Sinclair,  see  Sherman,  359 
Siven,  277,  336,  542 
Sjostrom,  143 
Skatol,  206 

Slack,  see  Benedict,  F.  G.,  133 
Sleep 
metabolism  during,  109,  no 
nitrogen  excretion  during,  table,  no 
Slemons,  387 
Slowtzoff,  326 
Smillie,  see  Folin,  449 
Smith,  see  Benedict,  F.  G.,  127 
Snapper,  523 
Soderstrom,  511 

see  Riche,  44,  63 
Sodium  benzoate,  hippuric  acid  from, 

185,  186 
Sodium  bicarbonate 

and   elimination  of   /2-oxybutyric 
acid,  484 

and  urinary  ammonia,  222 
Sodium  chlorid 

in  blood  in  pneumonia,  523 

daily  requirement  of,  359 

elimination  of,  167 

in  perspiration  in  nephritis,  496 

retention  in  fever,  522 
Sodium  urate 

lactam  form,  550 

lactim  form,  550 
Soetbeer,  547 
Soetbeer  and  Ibrahim,  538 
Soldner,  399 
"Somatose"  in  diet,  160 
Sonden  and  Tigerstedt,  in,  112 
Sonden, see  Johansson,  51,  87,  90 
Sorensen,  215 

Soy  bean,  glycinin,  comparative  value 
of,  in  growth,  376 


Specific  dynamic  action 
of  alanin,  240,  241 
of    alcohol    and    carbohydrate, 

357. 
of  amino-acids,  241,  243 

from  casein,  239 
of  carbohydrate,  237 

cause  of,  295 
of  casein,  239 
discovery  of,  43 
of  fat,  table,  237,  238,  252 
of  food-stuffs,  chart,  237 
of  food  in  typhoid  fever,  table, 

of  glutamic  acid,  240,  241 
of  glycocoll,  240,  241 
in  man,  239 
and  mass  action,  246 
of  "nutrose,"  406 
and  oxy-acids,  245 
of  protein,  232,  233,  234,  236 
cause  of,  244,  245 

views  of  Voit  and  Rubner. 
239 
intensity  of,  243 
in  pancreatic  glycosuria,  474 
in  phlorhizin  glycosuria,  474 
theory  of,  240 
of  various  proteins,  238 
Speck,  425 
Speed,  increase  in  metabolism  during, 

3^9,  330 
Spiro,  179,  421 
Spitzer,  531 
Spleen,   extirpation   of,   in   phlorhizin 

glycosuria,  451  • 

Squash-seed,    globulin,    comparative 

value  of,  in  growth,  376 
Ssubotin,  30 1 
Staeubli,  470,  486 
Stadelman,  465 
Staehelin,  504 

see  Falta,  239,  463,  474 
Starch  in  feces,  52 
Starvation,  see  Fasting 
Statistics,  food,  municipal,  table,  350 
Stearns,  see  Wilson,  444 
Steenbock,  Nelson,  and  Hart,  219 
Stepp,  W. 
effect  of 

addition  of  salts  and  fats  to  ex- 
tracted diet,  on  growth,  364 
feeding     alcohol-ether     extracted 
diet  to  mice,  364 
extraction  of  "accessory  substance" 
from  food,  364 
Stern,  see  Batelli,  192 
Steudel,  541 
see  Kossel,  528 


INDEX 


635 


Steyrer,  441 
Stiles  and  Lusk 

D  :  N  in  phlorhizin  glycosuria,  99, 

4S5  . 
after    ingestion   of   amino- 
acids,  172 
Stimulants  in  fatigue,  325 
Stimulation,     amino-acid,     action    on 

basal  metabolism,  301 
Stohmann,  37 

Stomach,  movements  of,  in  hunger,  70 
Stone-masons,  energy  requirements  of, 

349 
Straczewski,  see  Zeller,  199 
Strain,  effect  of,  on  metabolism,  322 
Straub 
carbon  monoxid  "diabetes,"  462 
water 
hunger,  69 

ingestion  on  protein  metabolism, 
162 
Strauss,  see  Abderhalden,  186 
Strohmer,  see  Meissl,  304 
Strychnin 
on  alkalinity  of  blood,  493 
on  basal  metabolism,  553 
and  body  glycogen,  107 
Stupor,  metabolism  in,  438 
Succinic  acid 

glucose  from,  202 
from  glutamic  acid,  202 
from  keto-glutaric  acid,  202 
Sucrose 
consumption   of,  in  United   States, 

561 
and  glycogen  oxidation,  289,  294 
Sugar,  see  Blood,  Diabetes,  and  vari- 
ous sugars. 
Sulphur 
ethereal,  formation  of,  207 
excretion  from  cystein,  200 
and  nitrogen  elimination,  167,  170; 

table,  168;  chart,  169 
and  nitrogen  in  urine  in  starvation, 

92 
urinary 

in  cystinuria,  199 
from  protein,  92 
Sumner,  see  Fiske,  81 
Sundstrom,  348 
Sunlight 

and  respiration,  150 
ultra-violet  rays  of,  effect  upon  met- 
abolism, 429 
Sunstroke,  definition  of,  499 
Surface  of  solids,  determination  of,  118 
Surface  area,  see  Area. 
Surra    trypanosomes,    metabolism    in 
fever  induced  by,  table,  504,  505 


Susruta,  445 

Suzuki,  Shimamura,  and  Odake,  367 

Sweat,  see  Water. 

Sweet  and  Ringer,  451 

Sydenham,  544 

Szalagyi  and  Kriwuscha,  541 


TACHAU,  496 

Tailors,  energy  requirements  of,  349 
Talbot,  see  Benedict,  F.  G.,  62,  406,  407 
Tallqvist,  270,  493 
Tangl 
action  of  chemical  stimulus,  246 
heat 

production  of  incubated  egg,  379 
value  of  urinary  nitrogen  on  high 
carbohydrate  diet,  38 
metabolism  of  fat  and  thin  pigs,  129 
statistics  of  absorption,  398 
Tangl  and  Mituch 

nitrogen  of  egg  during  incubation, 
380 
Taurin  from  cystein,  179,  199 
Tausz,  see  Galambos,  464 
Taylor,  556 

Taylor  and  Lewis,  81,  83 
Tea 
effect  of 

in  fatigue,  325 
on  purin  bases  in  urine,  532 
Temperature  (body), 
in  calorimetry,  133 
diurnal  variation,  in 
in  fasting,  in 
in  fever,  133,  505,  509 
of  frog,  114 

after  hot  baths,  500,  502 
of  internal  organs,  132,  134 
manner  of  heat  loss,  140 
on  protein  metabolism,  501 
and  purins,  501 
and  radiant  heat,  149 
rectal,  133 
regulation 

chemical,  118,  134,  141,  143 
and  blood  sugar,  145 
and  critical  temperature,  135 
and  hairy  covering,  136 
and  humidity,  147 
and  fat  ingestion,  252 
in  ichthyosis  hystrix,  500 
in  infant,  404 
and  protein  metabolism,  137, 

243 
physical,  118,  135,  138,  141 
in  fever,  510 
of  skin,  133 
Terray,  19 


636 


INDEX 


von  Terray,  427 

Terroine,  see  Armand-Delille,  285 

Tetanus,  effect  upon  glycogen  of  body, 

107 
Thannhauser 
action  of  human  duodenal  juice  on 
yeast  nucleic  acid,  530 
Thannhauser  and  Bommes 
uric  acid  excretion 

in  gout  after  injection  of 

adenosin,  548 
after  injection  of  adenosin 
and  guanosin,  539 
Theobromin,  fate  of,  532 
Theophyllin,  fate  of,  532 
Therapy,    x-ray,    effect    of,    in    lym- 
phatic leukemia,  425 
Thermometer  showing  comparison  of 
Fahrenheit  and  Centigrade  scales, 

573 
Thomas,  Karl 

absorption  of  milk,  354 

biologic  values  of  different  proteins, 

37i 
influence  of 

carbohydrate    on    nitrogen    equi- 
librium, 155 
fat  on  protein  retention,  254 
previous  high  protein  diet  upon 
nitrogen  elimination,  275 
metabolism  of  deposit  protein,  84 
nitrogen  equilibrium  with  low  nitro- 
gen intake,  278 
utilization  of  banana  protein,  355 
Thurlow,  see  Wilson,  <\.\/\ 
Thymin,  structure  of,  527 
Thymus,  ingestion  of,  and  uric  acid  in 

urine,  532 
Thyroid 
influence  of,  on  general  metabolism, 

439,  44° 
metabolism  after  removal  of,  440 
role  of,  in  diabetes,  459 
Thyroidectomy 

and  parathyroidectomy,  444 
in  phlorhizin  glycosuria,  461 
Thyroidin 
influence    of,    on    metabolism,  439, 
440 
Tichmeneff,  276 
Tigerstedt 
calcium  in  diet  of  Finns,  359 
effect    of    work    on    metabolism   in 

fasting,  109 
minimum    metabolism    of    man    at 

rest,  no 
see  Johansson,  51,  87,  90 
see  Rancken,  132 
see  Sonden,  in,  112 


Tissandier  and  Sivel's  balloon  ascen- 
sion, 426 

Tissue,  extract,  reaction  of,  217 

Tissues 
amino-acid  in,  80,  82 
diabetic,  /3-oxybutyric  acid  in,  467 
purin  content  of  various,  table,  541 
purin  enzymes  in,  533,  534,  535 
urea  in,  165 

Togel,  Brezina,  and  Durig,  290,  357 

Torok,  see  Benedikt,  H.,  480 

Toxins,   diphtheria  and   glycogen   re- 
tention, 522 
febrile,  mode  of  action,  509,  510 

Tracy  and  Clark,  210 

Training 

economy  of,  ^33 

effect  of,   upon  metabolism,  table, 

33i,  33.2 
effect  of,  in  mountain  climbing,  427, 

43i 
Transfusion,  see  Blood. 
Transition  period  of  protein  waste,  276 
Traube,  505 

Traube  and  Jochmann,  501 
Tributyrin,   splitting   of,  by  blood   of 

fasting  dog,  96 
Trioses,  lactic  acid  from,  265 

metabolism  of,  262 
Tryptophan 

conversion  to  kynurenic  acid,  81 

fate  of,  205 

indol  from,  206 

influence  of,  upon  growth,  372 

kynurenic  acid  from,  205,  206 

and  nitrogen  equilibrium,  159 

occurrence,  205 

/3-oxybutyric  acid  from,  205 

skatol  from,  206 
Tuberculosis,  toxic  destruction  of  pro- 
tein in,  513 
Tuczec,  91 

Turban,  see  Grafe,  284 
Turner,  Marshall,  and  Lamson,  82 
Turner,  see  Abel,  81 
Turpentine,  elimination   of,  in    urine, 

486 
Typewriting,  energy  requirement  for, 

349 
Tyrosin 
action  of  yeast  on,  180 
fate  of,  195 
glucose  from,  197 
homogentisic  acid  from,  178,  195 
occurrence  of,  195 
j'-oxybutyric  acid  from,  195,  197 
p-oxy-phenyl-lactic    acid    in    urine 

from,  181 
from  phenylalanin,  195,  196 


INDEX 


637 


UMBER  and  Retzlaff,  538 
Umber,  see  Klemperer,  490 
Underbill 

epinephrin  glycosuria,  461 
metabolism  after  administration  of 
hydrazin,  494 
Underhill  and  Blatherwick 

glucose  utilization   after  thyroid- 
ectomy, 444 
Underhill  and  Goldschmidt 

protein    sparing    by    ammonium 
citrate,  284 
Underhill  and  Hilditch 

glucose     utilization     after     thy- 
roidectomy, 444 
Underhill  and  Murlin 

respiratory  quotient  after  hydra- 
zin, 494 
Undernutrition 
energy  requirement  in,  101,  476 
low  level  of  nitrogen  equilibrium  in, 

279 
in  school  children,  cause  of,  559 
United   States,   food  supply,   cost  of, 

557 
Uracil,  structure  of,  527 
Urates,  allantoin  from,  535 

retention  of,  by  cartilage,  547 
Urea 

from  amino-acids,  176 
indications  of,  79 
from  ammonium  carbonate,  222 
from  d-arginin,  204 
in  blood 

in  nephritis,  405 
after  plasmapharesis,  83 
effect  of  ingestion  upon  heat  pro- 
duction, 231 
elimination 

affected  by  benzoate,  187,  188 

Ambard's  law,  165 

in  starvation  of  dog  after  meat, 

73,  74 
excretion  of,  in  fever,  501 
formation  of,  176 

by  liver,  222 
from  glycyl-glycin,  176 
heat  of  solution  of,  40 
production  and  nitrogen  excretion, 

165 

reversibility  in  organism,  165 

as    sparer    of    endogenous    protein 

metabolism,  284 
in  tissues,  165 
from  uric  acid,  533 
Uric  acid 

alcohol  on  excretion  of,  31,  545 

allantoin  from,  535,  536 

in  birds,  541 


Uric  acid 

in  blood 

chicken,  543 

in  gout,  547 

in  lead  poisoning,  547 

in  nephritis,  547 

normal,  547 

ox,  543 

after  purin  ingestion,  549 
from  caffein,  532 
combined  in  blood,  543 
constancy  of  excretion  of,  on  diet 

of,  340,  538 
in  Dalmatian  dog,  537 
discovery  of,   in   urinary  calculi, 

520 
drugs  on  elimination  of,  549 

elimination  of,  in  gout,  when  in- 
gested, 548 

endogenous,  539 

excretion  after  food,  540,  543 

exogenous,  539,  543 

fate  of,  ingested,  538 

formation,  531 

in  gout,  544,  548 

in  leukemia,.  547 

from  nucleo-proteins,  531,  547 

from  purin  bases,  531 

retention  in  gout,  548 

after  Rontgen  rays,  549 

structure  of,  527 

theoretic  formation  of,  527 

after  thymus  ingestion,  532 

from  tissue  extracts,  531 

urea  from,  535 
Uricase 

action  of,  536 
experiment  on,  536 
occurrence  of,  536,  538 
Urine 
aceton  excretion  in  starvation,  93, 

94 
acidity 

and  alveolar  carbon  dioxid   ten- 
sion, 218 

and  ash  of  foods,  361 
albumen  in,  in  starvation,  92 
allantoin  in,  535,  538 
amino-acids    in,    after    phosphorus 

poisoning,  492 
ammonia  in 

after  acid  ingestion,  table,  219,  220 

after  acid  phosphate  ingestion,  222 

after  Eck  fistula,  22 

after  fat  diet,  222 

effect  of  bladder  infection  on,  214 

and  food  intoxication  of  infants, 
220 

as  index  of  acid  formation,  214 


638 


INDEX 


Urine 

ammonia  in 

after  ingestion  of  sodium  bicar- 
bonate, 222 

1-arabinose  in,  487 

birds,  composition  of,  table,  541 

cadaverin  in,  203 

caloric  value,  38 

chemical   comparison  of,  on  purin- 
free  diets,  574 

in  chicken-pox,  524 

composition  of,  after  benzoate  feed- 
ing, table,  187 

creatin  in,  212 

diabetic,  absence  of  disaccharids  in, 

446  . 
diabetic,  amino-acids  in,  464 

first  glucose  identification  in,  446 

effect  of  water  drinking   on,  in   al- 
captonuria,  163 

elimination  of  chloral  in,  486 
of  camphor  in,  486 
of  turpentine  in,  486 

ethereal  sulphates,  formation  of,  207 

during  fasting,  Beaute's,  table,  92 

during  fever,  523 

formic  acid  in,  208 

fructose  in,  in  severe  diabetes,  446 

glucose  in,  in  anemia,  421,  422 

hydrogen-ion  concentration  of,  217 
on  a  mixed  diet,  361 
from  vegetarians,  361 

lactic  acid  in 

in  anemia,  421,  422 

in  asphyxia,  266 

in  oxygen  lack,  427 

after  phosphorus  poisoning.  263 

lactose  in,  396 

in  liver  cirrhosis,  181 

magnesium  and  nitrogen  in,  during 
fasting,  98 

in  measles,  524 

nitrogen . 

elimination  after  bloodletting,  84 
partition  on  different  diets,  209 
phosphorus  ratio  in  starvation,  92 
sulphur  ratio,  92 

/?-oxybutyric  acid  excretion  in  star- 
vation, 93,  94 

pentose  in,  487 

pig,  purin  bases  in,  534 

during   pregnancy,   composition  of, 

384 
purin  bases  in 

in  aseptic  fever,  523,  524 

in  fevers,  524 

of  various  animals,  table,  537 
putresin  in,  203 
reaction  of,  how  maintained,  214 


Urine 

d-ribose  in,  487 
in  scarlet  fever,  524 
sulphur  in,  in  cystinuria,  1-99 
sulphur  from  protein,  92 
titratible  acidity  of,  217 
uric  acid  in 

from  caffein,  532 

in  gout,  table,  548 

in  leukemia,  547 

after  thymus  ingestion,  532 
volume 

influence  of  glucose  feeding  on,  291 
and  nitrogen  from  each  kidney, 

165 
Urochrom  and  histidin,  205 
Uterus 
removal  of,  and  creatin  excretion,  212 


VALIN,  194 

aceton  bodies  from,  194,  195 
fate  of,  194 
glucose  from,  195 
Values,  standard,  of  food-stuffs,  42 
Van  Slyke 

method  of  investigating  intensity  of 
acidosis,  221 
Van  Slyke  and  Meyer 
amino-acids 
of  blood,  80 
of  liver,  81 
in  muscle,  80,  82 
of  tissues,  80 
Van  Slyke,  see  Osborne,  77 
Van  Slyke,  L.,  399 
Vedder,  E.  B.,  362,  366 
Veeder,  see  Du  Bois,  473 
Vegetable 

protein,  retention  of,  374 
proteins,  biologic  value  of,  table,  371 
Vegetables,  digestibility  of,  52 
Vegetarianism,    Graham's   system   of, 

338 

Vegetarians,  hydrogen-ion  concentra- 
tion of  urine  from,  361 

Verploegh,  see  Van  Hoogenhuyze,  210, 
212,  317 

Verzar,  448 

Viault,  435 

Vinograd,  see  Osborne,  77 

Vitamins,  363,  367,  378 
yeast,  composition  of,  378 
from  yeast,  use  of,  367 

Vividiffusion,  products  from,  82 

Voegtlin,  see  Koch,  367 

Voeltz  and  Dietrich,  357 

Voeltz  and  Paechtner,  397 

Vogt,  547 


INDEX 


639 


von  Voit,  Carl 

bile  solids  of  fasting  dog,  48 

bomb  calorimetry,  36 

chemical  regulation  during  mechan- 
ical work,  313 

"circulating  protein,''  74 

"Darmarbeit,"  231 

definition  of  a  food,  153 

discussion  of  metabolism,  45 

effect  of 

copious  water  drinking  on  protein 

metabolism,  162 
previous  diet  on  urea  elimination 

in  starvation,  73 
temperature    on    metabolism    in 
fasting,  142 

effect  on  metabolism  of  ingesting  in- 
creasing quantities  of  meat,  155 

fat  from  carbohydrate,  304 

glycogen    from    ingested    carbohy- 
drate, 258 

influence  of 

diet    on    composition    of     milk, 

fat  on  protein  metabolism,   248, 

249 
intensity  of  metabolism,  how  modi- 
fied, 239 
intermediary    protein    metabolism, 

171 
low  protein  diet,  343 
metabolism,  table  of,  36 
milk  nitrogen  and  urinary  nitrogen, 

39i 

muscle    work,    oxygen   supply   and 
metabolism,  30 

necrology  of  Pettenkofer,  29 

nitrogen 

equilibrium  in  dog  after  meat  in- 
gestion, 153,  163 
first  establishment  of,  21 

loss  of  nitrogen  in  hair  and  epidermis, 
22 

ration  of  average  laborer,  335 

''secondary  rise"  in  protein  metab- 
olism on  meat-fat  diet,  255 

value  of  Liebig's  extract,  352 

weight  loss  of  tissues  in  starvation, 

see  Bischoff,  24,  36,  48,  153,  156 
see  Pettenkofer,  25,  36,  37;  109,  223, 

228,  310,  424,  473 
see  Rauber,  150 
Voit,  E. 

effect  of  fat  in  starvation,  100 
general  table  of  starvation  metab- 
olism in  man,  90 
glycogen  in  goose  after  rice  inges- 
tion, 305 


Voit,  E. 

heat  production 

of  various  animals,  41 
resting  animals,  119 
increasing  metabolism  with  increas- 
ing temperature,  117 
influence  of  fat  upon  protein  metab- 
olism in  starvation,  100 
metabolism  of  pigeon  after  removal 

of  feathers,  138 
nitrogen     elimination     and     body 

weight,  85 
weight  loss  of  different  organs  in 

starvation,  105 
see  Frank,  120 
see  Lehmann,  305 
Voit,  E.,  and  Korkunoff 

influence    of'  carbohydrates    and 
protein  on  nitrogen  equilib- 
rium, 277 
of  fatonprotein'metabolism,  254 
nitrogen  equilibrium  in  dog  after 
meat  ingestion,  153 
Voit,  E.,  and  C.  Lehmann 

fat  from  carbohydrate,  305 
Voit,  F. 

metabolism  after  thyroid  ingestion, 

440 
proteolytic    cleavage    products    in 

dietetics,  160 
source  of  feces,  49 
temperature  on  nitrogen  elimination, 


WACKER,  449 

Wagner,  see  Parnas,  264 

Wakeman,  492 

Wakeman  and  Dakin,  197,  208,  466 

Waldvogel,  492 

Walking 

efficiency  during,  326 

horizontal,  influence  of  velocity  and 
load  upon  energy  requirements  in, 
328;  table,  329 

and  running,  comparison  of  energy 
requirements,  329 
Wallace  and  Salomon,  51 
Wallersteiner,  512 
Waltuch,  see  Zerner,  487 
Ward,  434 
Warkalla,  202 

Warmth  and  metabolism,  117 
Warren,  see  Ravold,  196 
Washburn,  see  Cannon,  70 
Washerwomen,    energy    requirements 

of,  340 
Waste  in  feces  of  herbivora.  51 

protein,  transition  period  of,  276 


640 


INDEX 


Water 
effect  of  ingestion  upon  heat  pro- 
duction, 231 
hunger,  definition  of,  69 
fatality  of,  70 
Straub's  experiment,  69 
loss  in  dietary  changes,  272,  273 

in  perspiration,  131,  132 
retention  in  fever,  522 
vaporized  by  lungs  and  skin,  131,  132 
Water  drinking,  162 
"Water  soluble  B,"  363 
Water  vaporization,  heat  of,  in  fever, 

511 
"Wear  and  tear"  protein  quota,  102 

definition  of,  275,  276 
effect  of  high  body  temperature 
and   increased   heat   produc- 
tion on,  501,  502 
irreducible  minimum  of,  282 
Weight 

loss  in  dietary  changes,  272,  273 
loss  in,  of  different  organs  during 

starvation,  table,  105 
to   surface,    constant,   for   different 
animals,  table,  119 
Weiland,  484 
Weinland 

fat  from  protein,  230 
ferments  from  living  ascaris,  305 
glycogen  from  galactose,  294 
Weintraud,  479 
Welch,  521 
Wells,  162 
von  Wendt 

influence   of   ingestion   of   salts   on 

composition  of  milk,  395 
nitrogen    and    sulphur    elimination 

after  meat  ingestion,  168 
retention    of    nitrogen,    iron,    and 
potassium  at  high  altitudes,  435 
Westenrijk,  see  Bernstein,  458 
Westhauser,  see  Morgan,  393 
Wheat 
embyro 

influence  of,  upon  growth,  370 
kernel 

entire,  influence  of,  upon  growth, 
37o 
proteins,  relative  value  of,  for  growth, 

375 
White,  400 

see  Mendel,  535 
Wiechowski 

action  of  dogs'  liver  upon  uric  acid, 

535 
allantoin,  538 
glycocoll,  186 
see  Knaffl-Lenz,  550 


Wiener,  534 

Wilenko,  see  Rona,  261,  468 

Willcock  and  Hopkins  372 

Williams,  44,  63 

Williams,  Riche,  and  Lusk,  224 

Williams  and  Seidell,  378 

Williams  and  Wolf,  199 

Willis,  Thomas,  445 

Wilson,  Margaret  B.,  410,  412 

Wilson,  Stearns,  and  Thurlow,  444 

von  Winckel,  384 

Wind 

and  heat  loss,  145 

influence   upon   metabolism,    table, 
146 
Wishart,  80 

see  Fisher,  G.,  291 
Wislicenus,  see  Fick,  315 
Wittenberg,  see  Embden,  265 
Wohl,  194,  265 
Wolf,  170 

see  Marriott,  199 

see  Williams,  199 
Wolff  berg,  171 
Wolgemuth,  492 
Wolpert,  145 

see  Broden,  313 
Women,  see  Lactation  and  Parturition. 

energy  requirements  of,  129,  349,  381 
Wood,  505 
Woodruff,  C.  E.,  150 
Woods  and  Mansfield,  320,  336,  348 
Wood-sawyers 

energy  requirements  of,  349 
Woodyatt 

glucose 

in  the  bile  after  phlorhizin,  451 
from  glyceric  aldehyd,  193 

lactic  acid  in  asphyxia,  266 

oxidation  of  glucose,  262 

see  Raulston,  484 

see  Sansum,  190 
Work,      mechanical,     see      Mountain 
climbing, 
and  altitude,  332,  429 
and  chemical  regulation,  313 
and  creatinin  elimination,  317 
and  diet,  311,  312 

various    food-stuffs,    311,    318, 

324 
energy  requirement 

light  work,  334 

same  work  by  different  ani- 
mals, 327 

under  various  conditions,  329 
and   environmental   temperature, 

312 
and  exhaustion,  321 
and  gradient,  330 


INDEX 


641 


Work,  mechanical 

maximum,  in  man,  321,  331,  431 
on  metabolism,  30,  309 
day  vs.  night,  109 
rapidity  of  effect,  325 
and  protein  metabolism,  108,  277, 
316 
in  phlorhizin  glycosuria,  458 
and  protein  retention,  317 
and  purin  elimination,  542 
and  respiratory  quotient,  321,  323 
urine  during,  317 
Wrestler,  trained,  maximum  amount  of 

work  attainable  by,  331 
Wright,  see  Cannon,  449 


XANTHIN,  fate  of  injected,  539 

oxidases,  532 

occurrence  of,  531,  533 

structure  of,  527 
Xanthosin,  guanosin  from,  530,  531 
1- Xylose,  from  d-glucuronic  acid,  487 

from  liver.  /187 


from  liver,  487 


Yeast 

in  diabetes,  485 

on  glutamic  acid,  202 

heat  production  and  surface  area, 

121,  122 
on  keto-glutaric  acid,  202 
on  oxy-aldehydes,  191 
on  p-oxy-phenyl-pyruvic  acid,  180 
protein,  synthesis  by,  285 
on  tyrosin,  180 
vitamins 

composition  of,  378 

from,  use  of,  367 

and  polyneuritis,  367 


ZACHARJEWSKI,  387 
Zein 

glucose  derivable  from,  457 

41 


Zein 

influence  of,  upon  growth,  372 
protein  sparing  by,  373 
Zeller,  270 

Zeller  and  Straczewski,  199 
Zerner  and  Waltuch,  487 
Ziegler,  521 
Zitowitsch,  358 
Zuntz 
anemia,  effect  of,  upon  glycogen,  421 
effect   of  air  rich  in   oxygen  upon 
oxygen  absorption,  419 
of  sunlight  upon  metabolism,  149 
of  training  upon  energy  require- 
ment, 332 
energy  requirement   in   undernutri- 
tion, 101 
heat  production  during  work,  318 
metabolism  and  speed,  330 
removal  of  glycogen  by  strychnin, 

107 
renal   character   of   phlorhizin   gly- 
cosuria, 450 
respiratory  quotient  for  human  fat, 

59 
see  Durig,  150,  427,  428,  430,  432, 

437 
see  Lehmann,  51,  59,  86,  no 
see  Ostertag,  385,  412 
see  Rohrig,  115,  120 
see  von  Mering,  231 
see  von  Schrotter,  428 
Zuntz,  Loewy,  Muller,  and  Caspari 

hemoglobin  at  high  altitudes, 

435 
metabolism  in  mountaineer- 
ing, 330 
Zuntz  and  Schumburg 

capacity  for  work  at  high  eleva- 
tions, 430 
heat  of  oxidation  of  fat  and  car- 
bohydrate, 62 
metabolism  in  marching,  331 
during  marching,  316 
Zuntz,  L.,  3ss,  381 
see  Loewy,  428,  432,  434 


SAUNDERS'  BOOKS 


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De  Lee's 
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Principles  and  Practice  of  Obstetrics.  By  Joseph  B.  De  Lee, 
M.  D.,  Professor  of  Obstetrics  in  the  Northwestern  University  Medical 
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The  Most  Superb  Book  on  Obstetrics  Ever  Published 

You  will  pronounce  this  new  book  by  Dr.  DeLee  the  most  elaborate,  the 
most  superbly  illustrated  work  on  Obstetrics  you  have  ever  seen.  Especially  will 
you  value  the  938  illustrations,  practically  all  original,  and  the  best  work  of  lead- 
ing medical  artists.  Some  175  of  these  illustrations  are  in  colors.  Such  a  mag- 
nificent collection  of  obstetric  pictures — and  with  really  practical  value — has  never 
before  appeared  in  one  book. 

You  will  find  the  text  extremely  practical  throughout,  Dr.  De  Lee's  aim  being  to 
produce  a  book  that  would  meet  the  needs  of  the  general  practitioner  in  every  par- 
ticular. For  this  reason  diagnosis  is  featured,  and  the  relations  of  obstetric  con- 
ditions and  accidents  to  general  medicine,  surgery,  and  the  specialties  brought  into 
prominence. 

Regarding  treatment :  You  get  here  the  very  latest  advances  in  this  field,  and  you 
can  rest  assured  every  method  of  treatment,  every  step  in  operative  technic,  is  just 
right.  Dr.  De  Lee's  twenty-one  years'  experience  as  a  teacher  and  obstetrician 
guarantees  this. 

.  Worthy  of  your  particular  attention  are  the  descriptive  legends  under  the  illus- 
trations. These  are  unusually  full,  and  by  studying  the  pictures  serially  with  their 
detailed  legends,  you  are  better  able  to  follow  the  operations  than  by  referring  to 
the  pictures  from  a  distant  text — the  usual  method. 

Dr.  M.  A.  Hanna,  University  Medical  College,  Kansas  City 

"  I  am  irank  in  stating  that  I  prize  it  more  highly  than  any  other  volume  in  my  obstetric 
library,  which  consists  of  practically  aU  the  recent  books  on  that  subject." 

Prof.  W.   Stoeckel,  Kiel,  Germany 

"  Dr.  DeLee's  Obstetrics  deserves  the  greatest  recognition.  The  text  and  the  913  very  beau- 
tiful illustrations  prove  that  it  is  written  by  an  obstetrician  of  ripe  experience  and  of  exceptional 
teaching  ability.     It  must  be  ranked  with  the  best  works  of  our  literature." 

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"  The  name  of  the  author  is  in  itself  a  sufficient  guarantee  of  the  merit  of  the  book,  and  I 
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GYNECOLOGY  AND    OBSTETRICS 


Bandler's 
Medical    Gynecology 


Medical  Gynecology.  By  S.  Wvllis  Bandler,  M.  D.,  Adjunct 
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for  him,  written  for  him,  and  illustrated  for  him.  There  are  many  gynecologic 
conditions  that  do  not  call  for  operative  treatment ;  yet,  because  of  lack  of  that 
special  knowledge  required  for  their  diagnosis  and  treatment,  the  general  practi- 
tioner has  been  unable  to  treat  them  intelligently.  This  work  not  only  deals 
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American  Journal  of  Obstetrics 

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Posterior  vaginal  celiotomy  is  of  great  importance  in  the  removal  of  small  tubal 
and  ovarian  tumors  and  cysts,  and  is  an  important  step  in  the  performance  of 
vaginal  myomectomy,  hysterectomy,  and  hysteromyomectomy.  Anterior  vaginal 
celiotomy  with  thorough  separation  of  the  bladder  is  the  only  certain  method 
of  correcting  cystocele. 

The  Lancet,  London 

"  Dr.  Bandler  has  done  good  service  in  writing  this  book,  which  gives  a  very  clear  descrip- 
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Strong  case  for  these  operations." 


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Ashton's 
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The  Practice  of  Gynecology.  By  W.  Easterly  Ashton,  M.  D., 
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rich  store-house  of  practical  information,  presented  in  such  a  way  that  the  work 
cannot  fail  to  be  of  daily  service  to  the  practitioner. 

Howard  A.  Kelly,  M.  D. 

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clear  and  satisfactory.  One  specially  good  feature  is  the  pains  with  which  you  describe  so 
many  details  so  often  left  to  the  imagination." 

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"  I  know  of  no  book  that  goes  so  thoroughly  and  satisfactorily  into  all  the  details  of  every, 
thing  connected  with  the  subject.     In  this  respect  your  book  differs  from  the  others." 

George  M.  Edebohls,  M.  D. 

Professor  of  Diseases  of  Women,  New  York  Post-Graduate  Medical  School 
"  A  text-book  most  admirably  adapted  to  teach,  gynecology  to  those  who  must  get  theil 
knowledge,  even  to  the  minutest  and  most  elementary  details,  from  books." 


GYNECOLOGY  AND    OBSTETRICS. 


Kelly  and  Cullen's 
Myomata   of  the  Uterus 


Myomataof  the  Uterus.  By  Howard  A.  Kelly,  M.  D.,  Professor 
of  Gynecologic  Surgery  at  Johns  Hopkins  University;  and  Thomas  S. 
Cullen,  M.  B.,  Associate  in  Gynecology  at  Johns  Hopkins  University. 
Large  octavo  of  about  700  pages,  with  388  original  illustrations,  by 
August  Horn  and  Hermann  Becker.  Cloth.  $7.50  net ;  Half  Morocco, 
$9.00  net. 

ILLUSTRATED     BY     AUGUST     HORN     AND     HERMANN     BECKER 

This  monumental  work,  the  fruit  of  over  ten  years  of  untiring  labors,  will 
remain  for  many  years  the  last  word  upon  the  subject.  Written  by  those  men 
who  have  brought,  step  by  step,  the  operative  treatment  of  uterine  myoma  to 
such  perfection  that  the  mortality  is  now  less  than  one  per  cent.,  it  stands  out  as 
the  record  of  greatest  achievement  of  recent  times. 

Surgery,  Gynecology,  and  Obstetrics 

"  It  must  be  considered  as  the  most  comprehensive  work  of  the  kind  yet  published.  It 
will  always  be  a  mine  of  wealth  to  future  students." 


Cullen's  Adenomyoma  of  the  Uterus 

Adenomyoma  of  the  Uterus.  By  Thomas  S.  Cullen,  M.B.  Octavo  of  275 
pages,  with  original  illustrations  by  Hermann  Becker  and  August  Horn.  Cloth, 
$5.00  net;  Half  Morocco,  $6.50  net. 

**  A  good  example  of  how  such  a  monograph  should  be  written.  Tt  is  an  excellent 
work,  worthy  of  the  high  reputation  of  the  author  and  of  the  school  from  which  it 
emanates." — The  Lancet,  London. 

Cullen's  Cancer  of  the  Uterus 

Cancer  of  the  Uterus.  By  Thomas  S.  Cullen,  M.B.  Large  octavo  of  693 
pages,  with  over  300  colored  and  half-tone  text-cuts  and  eleven  lithographs.  Cloth, 
$7.50  net ;  Half  Morocco,  $8.50  net. 

"  Dr.  Cullen's  book  is  the  standard  work  on  the  greatest  problem  which  faces  the 
surgical  world  to-day.  Any  one  who  desires  to  attack  this  great  problem  must  have 
this  book." — Howard  A.  Kelly,  M.  D.,  Johns  Hopkins  University. 


SAUNDERS'     BOOKS    ON 


Kelly  &  Noble's  Gynecology 
and  Abdominal  Surgery 

Gynecology  and  Abdominal  Surgery.  Edited  by  Howard  A. 
Kelly,  M.  D.,  Professor  of  Gynecology  in  Johns  Hopkins  University  ; 
and  Charles  P.  Noble,  M.  D.,  formerly  Clinical  Professor  of  Gyne- 
cology in  the  Woman's  Medical  College,  Philadelphia.  Two  imperial 
octavo  volumes  of  950  pages  each,  containing  880  illustrations,  some  in 
colors.     Per  volume:  Cloth,  $8.00  net ;  Half  Morocco,  $9.50  net. 

TRANSLATED  INTO  SPANISH 
WITH   880   ILLUSTRATIONS    BY  HERMANN   BECKER   AND   MAX   BRODEL 

In  view  of  the  intimate  association  of  gynecology  with  abdominal  surgery  the 
editors  have  combined  these  two  important  subjects  in  one  work.  For  this  reason 
the  work  will  be  doubly  valuable,  for  not  only  the  gynecologist  and  general  prac- 
titioner will  find  it  an  exhaustive  treatise,  but  the  surgeon  also  will  find  here  the 
latest  technic  of  the  various  abdominal  operations.  It  possesses  a  number  oi 
valuable  features  not  to  be  found  in  any  other  publication  covering  the  same  fields. 
It  contains  a  chapter  upon  the  bacteriology  and  one  upon  the  pathology  of  gyne- 
cology, dealing  fully  with  the  scientific  basis  of  gynecology.  In  no  other  work 
can  this  information,  prepared  by  specialists,  be  found  as  separate  chapters. 
There  is  a  large  chapter  devoted  entirely  to  medical  gynecology  written  especially 
for  the  physician  engaged  in  general  practice.  Abdominal  surgery  proper,  as  dis- 
tinct from  gynecology,  is  fully  treated,  embracing  operations  upon  the  stomach,  intes- 
tines, liver,  bile-ducts,  pancreas,  spleen,  kidneys,  ureter,  bladder,  and  peritoneum. 

Davis'  Manual  of  Obstetrics 

Dr.  Davis'  Manual  is  complete  in  every  particular  and  fully  illustrated  with 
original  line-drawings.  You  get  chapters  on  anatomy  of  the  normal  and  abnormal 
bony  pelvis,  physiology  of  impregnation,  anatomy  of  the  birth  canal  in  pregnancy, 
growth  and  development  of  the  embryo  ;  pregnancy,  its  diagnosis,  physiology, 
hygiene,  pathology  (complications)  ;  labor,  its  causes,  physiology,  pathology  (com- 
plications), management  ;  the  puerperal  period,  care  of  the  mother  and  infant  ; 
obstetric  asepsis  and  antisepsis  ;  obstetric  operations — use  of  forceps,  version,  em- 
bryotomy, prevention  and  repair  of  lacerations,  injury  to  the  bony  pelvis,  induc- 
tion of  labor,  cesarean  section  (abdominal  and  extraperitoneal),  symphysiotomy, 
pubiotomy,  lessening  size  of  sacral  promontory,  rupture  of  uterus  ;  fetal  pathology  ; 
injuries  to  fetus  in  labor  ;  mixed  feeding  ;  medicolegal  aspects. 

i2mo  of  463  pages,  with  171  original  line-drawings.  By  Edward  P.  Davis,  M.  D.,  Pro- 
fessor of  Obstetrics,  Jefferson  Medical  College,  Philadelphia.  Cloth,  $2.25  net. 


G  YNECOLOG  Y  AND   OBSTETRICS 


Webster's 
Text-Book  qf  Obstetrics 

A  Text=Book  of  Obstetrics.  By  J.  Clarence  Webster,  M.  D. 
(Edin.),  F.  R.  C.  P.  E.,  Professor  of  Obstetrics  and  Gynecology  in  Rush 
Medical  College,  in  affiliation  with  the  University  of  Chicago.  Octavo 
volume  of  767  pages,  illustrated.  Cloth,  $5.00  net;  Half  Morocco, 
$6.50  net. 

BEAUTIFULLY     ILLUSTRATED 

In  this  work  the  anatomic  changes  accompanying  pregnancy,  labor,  and  the 
puerperium  are  described  more  fully  and  lucidly  than  in  any  other  text-book  on 
the  subject.  The  exposition  of  these  sections  is  based  mainly  upon  studies  of 
frozen  specimens.  Unusual  consideration  is  given  to  embryologic  and  physiologic 
data  of  importance  in  their  relation  to  obstetrics. 

Buffalo  Medical  Journal 

"  As  a  practical  text-book  on  obstetrics  for  both  student  and  practitioner,  there  is  left  very 
little  to  be  desired,  it  being  as  near  perfection  as  any  compact  work  that  lias  been  published." 


Webster's 
Diseases   of  Women 

A  Text=Book  of  Diseases  of  Women.  By  J.  Clarence  Webster, 
M.  D.  (Edin.),  F.  R.  C.  P.  E.,  Professor  of  Gynecology  and  Obstetrics 
in  Rush  Medical  College.  Octavo  of  712  pages,  with  372  text-illustra- 
tions and  10  colored  plates.     Cloth,  $7.00  net;  Half  Morocco,  $8.50  net. 

Dr.  Webster  has  written  this  work  especially  for  the  general  practitioner,  dis- 
cussing the  clinical  features  of  the  subject  in  their  widest  relations  to  general 
practice  rather  than  from  the  standpoint  of  specialism.  The  magnificent  illus- 
trations, three  hundred  and  seventy-two  in  number,  are  nearly  all  original. 

Howard  A.  Kelly    M.  D. 

Professor  of  Gynecologic  Surgery,  Johns  Hopkins  University. 

"  It  is  undoubtedly  one  of  the  best  works  which  has  been  put  on  the  market  within  recent 
years,  showing  from  start  to  finish  Dr.  Webster's  well-known  thoroughness.  The  illustrations 
are  also  of  the  highest  order." 


SAUNDERS'   BOOKS   ON 


Hirst's 
Text-Book  of  Obstetrics 

Seventh    Edition 


A  Text=Book  ot  Obstetrics.  By  Barton  Cooke  Hirst,  M.D., 
Professor  of  Obstetrics  in  the  University  of  Pennsylvania.  Handsome 
octavo  of  1013  pages,  with  895  illustrations,  53  of  them  in  colors. 
Cloth,  $5.00  net ;  Half  Morocco,  $6.50  net. 

INCLUDING  RELATED  GYNECOLOGIC  OPERATIONS 

Immediately  on  its  publication  this  work  took  its  place  as  the  leading  text-book 
on  the  subject.  Both  in  this  country  and  in  England  it  is  recognized  as  the  most 
satisfactorily  written  and  clearly  illustrated  work  on  obstetrics  in  the  language. 
The  illustrations  form  one  of  the  features  of  the  book.  They  are  numerous  and 
the  most  of  them  are  original.  In  this  edition  the  book  has  been  thoroughly  revised. 
Recognizing  the  inseparable  relation  between  obstetrics  and  certain  gynecologic 
conditions,  the  author  has  included  all  the  gynecologic  operations  for  complica- 
tions and  consequences  of  childbirth,  together  with  a  brief  account  of  the  diagnosis 
and  treatment  of  all  the  pathologic  phenomena  peculiar  to  women. 


OPINIONS  OF  THE   MEDICAL  PRESS 


British  Medical  Journal 

"  The  popularity  of  American  text-books  in  this  country  is  one  of  the  features  of  recent 
years.  The  popularity  is  probably  chiefly  due  to  the  great  superiority  of  their  illustrations 
over  those  of  the  English  text-books.  The  illustrations  in  Dr.  Hirst's  volume  are  far  more 
numerous  and  far  better  executed,  and  therefore  more  instructive,  than  those  commonly 
found  in  the  works  of  writers  on  obstetrics  in  our  own  country." 

Bulletin  of  Johns  Hopkins  Hospital 

"The  work  is  an  admirable  one  in  every  sense  of  the  word,  concisely  but  comprehensively 
written." 

The  Medical  Record,  New  York 

**  The  illustrations  are  numerous  and  are  works  of  art,  many  of  them  appearing  for  the  first 
time.  The  author's  style,  though  condensed,  is  singularly  clear,  so  that  it  is  never  necessary 
to  re-read  a  sentence  in  order  to  grasp  the  meaning.  As  a  true  model  of  what  a  modern  text- 
book on  obstetrics  should  be,  we  feel  justified  in  affirming  that  Dr.  Hirst's  book  :s  without  a 
rival." 


DISEASES    OE    WOMEN. 


HirstV 
Diseases  of  Women 


A  Text=Book  of  Diseases  of  Women.  By  Barton  Cooke  Hirst, 
M.  D.,  Professor  of  Obstetrics,  University  of  Pennsylvania ;  Gynecolo- 
gist to  the  Howard,  the  Orthopedic,  and  the  Philadelphia  Hospitals. 
Octavo  of  745  pages,  with  701  original  illustrations,  many  in  colors. 
Cloth,  $5.00  net;  Half  Morocco,  $6.50  net. 

SECOND  EDITION— WITH  701  ORIGINAL  ILLUSTRATIONS 

The  new  edition  of  this  work  has  just  been  issued  after  a  careful  revision. 
As  diagnosis  and  treatment  are  of  the  greatest  importance  in  considering  diseases 
of  women,  particular  attention  has  been  devoted  to  these  divisions.  To  this  end, 
also,  the  work  has  been  magnificently  illuminated  with  701  illustrations,  for  the 
most  part  original  photographs  and  water-colors  of  actual  clinical  cases  accumu- 
lated during  the  past  fifteen  years.  The  palliative  treatment,  as  well  as  the 
radical  operative,  is  fully  described,  enabling  the  general  practitioner  to  treat 
many  of  his  own  patients  without  referring  them  to  a  specialist.  An  entire  sec- 
tion is  devoted  to  a  full  description  of  all  modern  gynecologic  operations,  illumi- 
nated and  elucidated  by  numerous  photographs.  The  author's  extensive  ex- 
perience renders  this  work  of  unusual  value. 


OPINIONS  OF  THE  MEDICAL  PRESS 


Medical  Record,  New  York 

"  Its  merits  can  be  appreciated  only  by  a  careful  perusal.  .  .  .  Nearly  one  hundred  pages 
are  devoted  to  technic,  this  chapter  being  in  some  respects  superior  to  the  descriptions  in 
many  other  text-  boks." 

Boston  Medical  and  Surgical  Journal 

"The  author  has  given  special  attention  to  diagnosis  and  treatment  throughout  the  book, 
and  has  produced  a  practical  treatise  which  should  be  of  the  greatest  value  to  the  student,  the 
general  practitioner,  and  the  specialist." 

Medical  News,  New  York 

"  Office  treatment  is  given  a  due  amount  of  consideration,  so  that  the  work  will  be  as 
useful  to  the  non-operator  as  to  the  specialist." 


SAUNDERS'    BOOKS   ON 


GET  i»  #  THE  NEW 

THE  BEST  /\  HI  6  f  1  C  Si  II  STANDARD 

Illustrated   Dictionary 

New  (8th)    Edition— 1500  New  Words 


The  American  Illustrated  Medical  Dictionary.  A  new  and  com- 
plete dictionary  of  the  terms  used  in  Medicine,  Surgery,  Dentistry, 
Pharmacy,  Chemistry,  Veterinary  Science,  Nursing,  and  kindred 
branches;  with  over  100  new  and  elaborate  tables  and  many  handsome 
illustrations.  By  W.  A.  Newman  Dorland,  M.D.,  Editor  of  "The 
American  Pocket  Medical  Dictionary."  Large  octavo,  1 137  pages, 
bound  in  full  flexible  leather.  Price,  $4.50  net;  with  thumb  index, 
$5.00  net. 

IT  DEFINES  ALL  THE  NEW  WORDS— MANY  NEW  FEATURES 

The  American^Illustrated  Medical  Dictionary  defines  hundreds  of  the  newest 
terms  not  defined  in  any  other  dictionary — bar  none.  These  new  terms  are  live, 
active  words,  taken  right  from  modern  medical  literature. 

It  gives  the  capitalization  and  pronunciation  of  all  words.  It  makes  a  feature 
of  the  derivation  or  etymology  of  the  words.  In  some  dictionaries  the  etymology 
occupies  only  a  secondary  place,  in  many  cases  no  derivation  being  given  at  all. 

In  the  "American  Illustrated"  practically  every  word  is  given  its  derivation. 

Every  word  has  a  separate  paragraph,  thus  making  it  easy  to  find  a  word 

quickly. 

The  tables  of  arteries,  muscles,  nerves,  veins,  etc.,  are  of  the  greatest  help 
in  assembling  anatomic  facts.  In  them  are  classified  for  quick  study  all  the 
necessary  information  about  the  various  structures. 

Every  word  is  given  its  definition — a  definition  that  defines  in  the  fewest  pos- 
sible words.  In  some  dictionaries  hundreds  of  words  are  not  defined  at  all,  refer- 
ring the  reader  to  some  other  source  for  the  information  he  wants  at  once. 

Howard  A.  Kelly,  M.  D.,  Johns  Hopkins  University,  Baltimore 

"  The  American  Illustrated  Dictionary  is  admirable.  It  is  so  well  gotten  up  and  of  such 
convenient  size.     No  errors  have  been  found  in  my  use  of  it." 

J.  Collins  Warren,  M.  D„  LL.D.,  F.R.C.S.  (Hon.),  Harvard  Medical  School 

"  I  regard  it  as  a  valuable  aid  to  my  medical  literary  work.  It  is  very  complete  and  of 
convenient  size  to  handle  comfortably.     I  use  it  in  preference  to  any  other." 


GYNECOLOGY  AND    OBSTETRICS  it 

Penrose's 
Diseases  of  Women 

Sixth    Revised    Edition 


A  Text=Book  of  Diseases  of  Women.  By  Charles  B.  Penrose, 
M.  D.,  Ph.  D.,  formerly  Professor  of  Gynecology  in  the  University  of 
Pennsylvania ;  Surgeon  to  the  Gynecean  Hospital,  Philadelphia.  Oc- 
tavo volume  of  550  pages,  with  225  fine  original  illustrations.     Cloth, 

$3-75  net- 

ILLUSTRATED 

Regularly  every  year  a  new  edition  of  this  excellent  text-book  is  called  for, 
and  it  appears  to  be  in  as  great  favor  with  physicians  as  with  students.  Indeed, 
this  book  has  taken  its  place  as  the  ideal  work  for  the  general  practitioner.  The 
author  presents  the  best  teaching  of  modern  gynecology,  untrammeled  by  anti- 
quated ideas  and  methods.  In  every  case  the  most  modern  and  progressive 
technique  is  adopted  and  made  clear  by  excellent  illustrations. 

Howard  A.  Kelly,  M.D.. 

Professor  of  Gynecologic  Surgery,  Johns  Hopkins  University,  Baltimore. 
"  I  shall  value  very  highly  the  copy  of  Penrose's  '  Diseases  of  Women '  received.     I  have 
already  recommended  it  to  my  class  as  THE  BEST  book." 


Davis'  Operative  Obstetrics 

Operative  Obstetrics,  By  Edward  P.  Davis,  M.D.,  Professor  of 
Obstetrics  at  Jefferson  Medical  College,  Philadelphia.  Octavo  of  483 
pages,  with  264  illustrations.     Cloth,  $5.50  net;  Half  Morocco,  $7.00  net. 

INCLUDING  SURGERY  OF  NEWBORN 

Dr.  Davis'  new  work  is  a  most  practical  one,  and  no  expense  has  been  spared 
to  make  it  the  handsomest  work  on  the  subject  as  well.  Every  step  in  every 
operation  is  described  minutely,  and  the  technic  shown  by  beautiful  new  illustra- 
tions.    Dr.  Davis'  name  is  sufficient  guarantee  for  something  above  the  mediocre. 


S.lf.VDEAS'    BOOKS    ON 


Norris* 
Gonorrhea  in  Women 

Gonorrhea  in  Women.  By  Charles  C.  Norris,  M.  D.,  Instructor 
in  Gynecology,  University  of  Pennsylvania.  With  an  Introduction  by 
John  G.  Clark,  M.  D.,  Professor  of  Gynecology,  University  of  Penn- 
sylvania.    Large  octavo  of  520  pages,  illustrated.  Cloth,  $6.50  net. 

A    CLASSIC 

Dr.  Norris  here  presents  a  work  that  is  destined  to  take  high  place  among 
publications  on  this  subject.  He  has  done  his  work  thoroughly.  He  has  searched 
the  important  literature  very  carefully,  over  2300  references  being  utilized.  This, 
coupled  with  Dr.  Norris'  large  experience,  gives  his  book  the  stamp  of  authority. 
The  chapter  on  serum  and  vaccine  therapy  and  organotherapy  is  particularly 
valuable  because  it  expresses  the  newest  advances.  Every  phase  of  the  subject 
is  considered  :  History,  bacteriology,  pathology,  sociology,  prophylaxis,  treatment, 
gonorrhea  during  pregnancy,  parturition  and  puerperium,  and  all  other  phases. 


AshtOn'S    Obstetrics  New  (8th)  Edition 

Essentials  of  Obstetrics.  By  W.  Easterly  Ashton,  M.  D. 
Revised  by  John  A.  McGlinn,  M.D.  i2mo  of  287  pages,  109  illus- 
trations.    Cloth,  $1.25  net.      In  Saunders'  Question-Compend  Series. 

Schaffer  &  Webster's  Operative  Gynecology 

Atlas    and    Epitome    of    Operative    Gynecology.      By  Dr.  O. 

Schaffer,  of  Heidelberg.  Edited,  with  additions,  by  J.  Clarence 
Webster,  M.D.  (Edin.),  F.  R.  C.  P.  E.  138  pages,  illustrated. 
Cloth,  $3.00  net.      In  Saunders'  Hand-Atlas  Series. 

Cragin's  Gynecology  New  (8th)  Edition 

Essentials  of  Gynecology.  By  Edwin  B.  Cragin,  M.D.  Re- 
vised by  Frank  S.  Mathews,  M.  D.  Crown  octavo,  232  pages, 
59  illustrations.  Cloth,  $1.25  net.  In  Saunders'  Question-Compend 
Series. 

American  Pocket  Dictionary  New  (9th)  Edition 

The  American  Pocket  Medical  Dictionary.  Edited  by  W.  A. 
Newman  Dorland,  A.M.,  M.  D.  693  pages.  $1.25  net;  with 
patent  thumb  index,  $1.50  net. 


GYNECOLOGY  13 


Montgomery's  Care  of  Surgical  Patients 

Care  of  Patients  Undergoing  Gynecologic  and  Abdominal  Procedures 
Before,  During,  and  After  Operation.  By  E.  E.  Montgomery,  A  .M., 
M.  D.,  LL.  D.,  F.  A.  C.  S.,  Professor  of  Gynecology  in  Jefferson  Medical  Col- 
lege, Philadelphia.       nmo  of  149  pages,  illustrated.      Cloth,  $1.25  net. 

Every  abdominal  operation  is  definitely  covered,  and  each  step  in  it  set  down  in 
detail,  giving  the  reasons  for  every  procedure.  The  duties  of  the  nurse  and  the 
assistants  are  explained  clearly,  giving  you  detailed  instruction  and  specific  fnforma- 
tion  on  every  operation  in  the  field  of  gynecologic  and  abdominal  surgery.  It  is  a 
book  to  lessen  your  labor  and  increase  your  efficiency.  It  is  pre-  and  post-operative 
care  complete. 


Schaffer     and     Edgar's     Obstetric      Diagnosis     and 
Treatment 

Atlas  and  Epitome  of  Obstetric   Diagnosis  and    Treatment.     By  Dr. 

O.  Schaffer,  of  Heidelberg.  Edited,  with  additions,  by  J.  Clifton  Edgar, 
M.  D.(  Professor  of  Obstetrics  and  Clinical  Midwifery,  Cornell  University 
Medical  School,  New  York.  With  122  colored  figures  on  56  plates,  38  text- 
cuts,  and  315  pages  of  text.      Cloth,   $3.00  net.      Saunders   Hand-Atlases. 


Schaffer  and  Norris'  Gynecology 

Atlas  and  Epitome  of  Gynecology.  By  Dr.  O.  Schaffer,  of  Heidel- 
berg. Edited,  with  additions,  by  Richard  C.  Norris,  A.  M.,  M.  D., 
Gynecologist  to  Methodist  Episcopal  and  Philadelphia  Hospitals.  With  207 
colored  figures  on  90  plates,  65  text-cuts,  and  308  pages  of  text.  Cloth, 
#3. 50  net.      ///  Saunders'  Hand-Atlas  Series. 


Galbraith's  Four  Epochs  of  Woman's   Life 

New  (3d)  Edition 

The  Four  Epochs  of  Woman's  Life :  A  Study  in  Hygiene.  By  Ann4 
M.  Galbraith,  M.  D.,  Fellow  of  the  New  York  Academy  of  Medicine,  etc 
With  an  Introductory  Note  by  John  H.  Musser,  M.  D.,  University  of 
Pennsylvania.      i2mo  of  296  pages.      Cloth,  Si.  50  net. 

Birmingham  Medical  Review,   England 

"  We  do  not,  as  a  rule,  care  for  medical  books  written  for  the  instruction  of  the  public. 
But  we  must  admit  that  the  advice  in  Dr.  Galbraith's  work  is,  in  the  main,  wise  and 
wholesome." 


DATE  DUE 


OCMCO  38-296 


;,^^^^|r 


Lusk  L97 

The  science  of  nutrition  1917 


